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Make sure Quotas and Power management are not set to power down, hibernate, stop access or disconnect the volume for any reason. Also, make sure the system is not set to hibernate itself.
This may sound strange but it is true, eSATA cables actually have compatibility issues. Just because one eSATA cable works between a pair of computers doesn't mean that cable will function between another pair. This is because they are handling such high-speed signals that even the most minor differences between physical characteristics are magnified and can become unreliable paths for the signal to follow and thus can fall into margins of partial functionality causing bazaar symptoms or no apparent equipment connection.
Additionally, USB and, especially eSATA cables, are cables which carry these very high speed signals with multiple conductors and shielding. And, like most manufacturers, the cables we ship are tested by the cable manufacturer but they are not tested again by us - that would increase costs dramatically. Because the signals in eSATA cables are almost 6 times faster than USB 2.0, eSATA cables are especially very susceptible to the effects of simple folding, or fracture during installation and often there is no external evidence suggesting such. A fracture or defect in shielding can cause total failure, intermittent function or strange inconsistent symptoms due to those high speed signals used in them and their production of, and susceptibility to, RFI. Because we do not ship multiples of USB and eSATA cables with our equipment, often if there is a cable failure or compatibility, it is overlooked because there is not an alternate cable to try during tech support diagnostic routines. Furthermore, if replacement equipment is sent due to assumed failure, even though the replacement equipment is shipped with a replacement eSATA or USB, often the installing technician will overlook replacing the cables and may determine that the replacement equipment has failed as well. Replace the cables with the replacement equipment. Second, we suggest installers carry extra eSATA and USB cables with them which they know function for diagnostic purposes. AS A RULE, SHORTER CABLES ARE ALWAYS BETTER THAN LONGER ONES, especially with high speed signals. If you have a shorter cable you can change out for a longer one, do so.
If you're using backup software, call technical support for the backup software maker to confirm that you have set up the software correctly.
Does it work on another machine without falling off? Move the High-Rely unit to another computer, is the result exactly the same? If so, this indicates the problem is somewhere with the high-rely equipment. If not, it is likely a problem with your host.
Are you using Disk Management (right click my computer, select manage, select disk management) to check for the actual volumes? If the drive is physically recognized by the host and showing in Disk Management, but there is no drive letter, then it is likely that hardware is fine. Consider using our HRDM2 utility to assign drive letters. Also, if you're assigning drive letters but they're not sticking after you remove and replace the drive, from the command prompt type "mountvol /E".
Is there a network drive or other drive mapped over one of the High-Rely drives? This will make things very confusing and cause the HR volume to lose its volume letter or have it reassigned.
Does it work on USB? If you have the option to test the device on USB and it works, that will at least tighten the problem to something related to the SATA/Controller side.
Completely uninstall and reinstall the drivers. The drivers maybe correct but something has since changed in the machine and the resources the driver is using are in conflict. Uninstall the drivers and reinstall. If possible, uninstall the drivers, remove the controller card. Boot the machine and shut down. Reinstall the controller card and then reinstall the drivers.
Try moving the controller card to another slot. A lot of times the machine will allocate resources which are in conflict with other devices. This is very common on Dell servers.
Uninstall the controller in the control panel. Power off the machine. Power on the machine and let it boot without the SATA controller present. Then shut it down again, power it off, reinstall the controller and reinstall the drivers. Sometimes other drivers muck with the resources and conflicts occur. Doing this will "re-shuffle" the resources.
Are you using the correct drivers? Some Microsoft updates have actually updated the SATA drivers to later versions which actually have problems. COMPLETELY Uninstall the current drivers and reinstall the correct ones.
Change Media - it could be the media itself. This is quite common. If you're rotating media, one piece of media in the rotation can be bad and cause the appearance of system wide troubles if you're not paying attention to which media the failure keeps occurring on. Disk check all media. When a piece of media fails or drops out, put a temporary sticker on it to mark and and see if it happens to the same piece of media again on the next rotation.
Change unit (usually not the fix). The number one assumption from customers with troubles is that the High-Rely hardware has failed. However in the instance of customers with troubles who have exchanged hardware, only 30% of the returned hardware is ever confirmed as defective meaning that the customer wasted time and money only to later find a different issue to be the cause. But, there are instances where the High-Rely's failure can not be argued - for example no power, no indicator lights.
Change the controller (usually not the fix). The number one assumption from customers with troubles is that the High-Rely hardware has failed. However in the instance of customers with troubles who have exchanged hardware, only 30% of the returned hardware is ever confirmed as defective meaning that the customer wasted time and money only to later find a different issue to be the cause. But, there are instances where the High-Rely's failure can not be argued - for example no power, no indicator lights.
Slimline problems. Often a new Slimline is sent out and the customer complains that the problem is persisting. Because the Slimline has an external power supply, often the customer only replaces the Slimline unit and never thinks to exchange the power supply as well. As the power supply is the most critical of the electronics for the Slimline, this should be the first concern.
Are you using a BE Backup-to-Disk folder instead of a Removable B2D? (BE will say the drive is offline) Is the problem occurring on swap, with the drive letter not mounting? (Usually WinServer Enterprise Ed.) Has the drive been setup as a Dynamic disk for creating a raid etc? (Windows will indicate offline in Disk Management).
Are the cables good and are they fully inserted? An obvious question but often overlooked. Replace or exchange cables. Also, ensure that power cable is fitted securely and that you have the unit plugged into stable UPS system. Be sure to check cable connections at server and unit side as well.
Does the media pass a chkdisk utility? Quick tests may show the media is fine but a suspect media should be chkdisked.
What errors if any is showing the system log or the error log for the specific back up software. Is windows reporting a corrupt file on the high-rely drive? Additional clues can be here.
A common problem with newer Dell servers using a PCI-E eSATA controller is that the controller will not show up in the hardware list as a mass storage controller, rather, it appears under the AHCI ATA Drive, even though the unit may not have any ATA drives in it. None-the-less, this is the device to install the PCI-E eSATA controller driver to. It should appear and work properly after that. Most Dell servers can not have the AHCI function disabled.

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