A lost cluster (which is also known as a lost file fragment) appears to Windows as in use, but it does not have a file associated with it. Programs such as ScanDisk and Norton Disk Doctor find and fix lost clusters.
What causes lost clusters? Crashes, mostly - by Windows and by applications. If a program crashes while it is creating, copying, or enlarging a file, some of the file's clusters may not be re-marked as available, even though the file with which the clusters are associated no longer uses or needs them. That leaves clusters marked as in use, but with no files or other clusters pointing to them.
A loose or defective drive cable can also cause lost clusters by creating bad sectors within clusters. If your system and applications don't crash often but you still end up with lost clusters, try removing your PC's case and checking the ribbon cables running between the drives and the motherboard. I know of no way a bad drive by itself could cause lost clusters, however.
In theory, you could lose clusters by defragging your drive while running other applications, although today's defraggers make that unlikely. Still, it's safer to defragment your hard drive with no other programs open.
When a disk scanner finds a lost cluster, it gives you two options: save the contents of the cluster as a file so you can look at it and decide if you need it, or mark the cluster as unused to free up wasted disk space.
The safest option is to save the contents as a file, but I have never found anything worth saving in a lost cluster, and I stopped saving them years ago. They virtually always contain extra copies of information that is safely stored elsewhere on the drive.