As seen on Apple’s website

To start up into Safe Mode (to Safe Boot), do this:

  1. Be sure your Mac is shut down.
  2. Press the power button.
  3. Immediately after you hear the startup tone, hold the Shift key. The Shift key should be held as soon as possible after the startup tone, but not before the tone.
  4. Release the Shift key when you see the gray Apple icon and the progress indicator (looks like a spinning gear).

During startup in Mac OS X v10.4 through Mac OS X v10.6.8, you will see “Safe Boot” on the login window, which appears even if you normally log in automatically. During startup in Mac OS X v10.2 through v10.3.9, you will see “Safe Boot” on the Mac OS X startup screen.

To leave Safe Mode, restart the computer normally, without holding any keys during startup.

 

Other interesting boot modes:

Press C during startup Start up from a bootable CD or DVD, such as the Mac OS X Install disc that came with the computer.
Press D during startup Start up in Apple Hardware Test (AHT).
Press Option-Command-P-R until you hear startup sound a second time. Reset NVRAM
Press Option during startup Start up in Startup Manager, where you can select a Mac OS X volume to start from. Note: Press N to make the the first bootable Network volume appear as well.
Press Eject, F12, or hold the mouse or trackpad button Ejects any removable media, such as an optical disc.
Press N during startup Attempt to start up from a compatible network server (NetBoot).
Press T during startup Start up in Target Disk Mode.
Press Shift during startup Start up in Safe Boot mode and temporarily disable login items.
Press Command-V during startup Start up in Verbose mode.
Press Command-S during startup Start up in Single-User mode.
Press Option-N during startup Start from a NetBoot server using the default boot image.
Press Command-R during startup Start from Lion Recovery1