First, if at all possible make a backup of the drive in its present configuration. If something goes wrong during repair attempts and makes things worse you will have a backup. You will have to decide how to work this in the light of any present backups you may have, for example, a backup that may be a few days out of date. In that case you may want to keep that one and make a second backup of this as they are now, though I realize people often don't have a lot of empty drives sitting around.
Boot from the System Installer disc that came with your computer or is the one for the version you currently have on there, select language if applicable, choose utilities, run Disk Utility and verify (and repair if necessary) the drive. You can verify a drive from DU on your main drive while booted but I have found this can result in incorrect reporting of errors. To repair your drive you have to run it from a drive other than the boot drive anyway.
Next, boot from your drive in [Safe Mode|http://docs.info.apple.com/article.html?artnum=107393] and repair permissions. You can repair permissions while booted from the installer disc but this uses the permissions configuration on the installer disc which may be out of date if you have run any updates on your computer. Booting your computer to Safe Mode restricts the number of things running on your computer while permissions are being run and does a bit of spring cleaning at the same time.
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[Resolve startup issues and perform disk maintenance with Disk Utility and fsck|http://docs.info.apple.com/article.html?artnum=106214]
[Using Disk Utility in Mac OS X 10.4.3 or later|http://docs.info.apple.com/article.html?artnum=302672]
[Disk Utility's Repair Disk Permissions 10.0-10.6|http://docs.info.apple.com/article.html?artnum=25751]
"Try Disk Utility" (modified from [http://support.apple.com/kb/TS1417])
1. Insert the Mac OS X Install disc that came with your computer (Edit: Do not use this disc if it is not the same general version as what you have currently on your computer, e.g. use a Tiger disc for a Tiger drive, not a Panther disc), then restart the computer while holding the C key.
2. When your computer finishes starting up from the disc, choose Disk Utility from the Installer menu. (In Mac OS X 10.4 or later, you must select your language first.)
Important: Do not click Continue in the first screen of the Installer. If you do, you must restart from the disc again to access Disk Utility.
3. Click the First Aid tab.
4. Click the disclosure triangle to the left of the hard drive icon to display the names of your hard disk volumes and partitions.
5. Select your Mac OS X volume.
6. Click Repair. Disk Utility checks and repairs the disk."
Then boot in Safe Mode, (holding Shift key down at bootup; takes longer to boot this way so be patient), run Disk Utility in Applications>Utilities, then highlight your drive, click on Repair Permissions, reboot when it completes.
[Mac OS X: Starting up in Safe Mode|http://docs.info.apple.com/article.html?artnum=107393]
[What is Safe Boot, Safe Mode? (Mac OS X)|http://support.apple.com/kb/HT1564]
[Safe Boot takes longer than normal startup|http://docs.info.apple.com/article.html?artnum=107394]
[Mac OS X 10.4, 10.5- Computer shuts down during Safe Boot|http://support.apple.com/kb/TA24054]