If you are running FAT or FAT32 (Windows 95,98 & ME)partitions then defragmentation is essential on a busy PC to keep it in peak condition.
With NTFS partitions the situation is less clear. When Microsoft released Windows NT, they insisted that it would never need defragmenting - but they were soon proved wrong. Windows 2000 and XP is supplied with a defrag program to address this.
As with anything, there are two sides to the argument. I personally believe that there is some slight improvement in speed when you defrag a heavily fragmented drive, even on NTFS.