In Disk Utility (Utilities folder) select the drive in the left column (the drive, all the way at the left, not the volume indented below it).
At the bottom of the window make sure "S.M.A.R.T. Status" shows "Verified". This means the drive is not indicating any hardware errors.
In the "First Aid" tab, click the "Verify" button to check the directory structure.
Click the "Repair Permissions" button to check permissions on system files. This may generate a lot of error messages, but they can be ignored. If you run it a second time, most will be gone.
<http://support.apple.com/kb/TS1448>
Defragmentation is not recommended.
The important thing is to always have good backups, via Time Machine or other methods. A drive can fail at any time, with no warning.