I am running Visual Studio 2008 with SP1. When I debug an application, it will skip over my break points.
For example, I have two lines of code, each call a method.
In addition to the above methods, I've also come across another couple of circumstances where breakpoints aren't hit:
trunk and branch dir that I swapped around and VS opened files in the other directory.mspdbsrv.exe is still attached to it, so check your process list. Restart Visual Studio often fixes this.