Solution 1:

I had the same problem but a different solution. Please note I updated to VS 2015 Update 1 and the problem is still there.

In previous edition of VS starting debug automatically triggered a build in debug mode. But with VS2015 it does not.

So if your last build was in release mode, and you try debugging, breakpoint won't work.

You have to manually build in debug mode first, then start debugging.

Solution 2:

I had the same problem.

I solved it disabling "Optimize code" option in project properties Build tab.

Solution 3:

This may seem trivial, but after a lot of headscratching with the same issues as you mention, I found out that my build was set to "release" instead of "debug" when I tried debugging.. re-building the solution for "debug" fixed it, and I could set breakpoints as normal

Solution 4:

I had a similar issue with breakpoints failing to bind, as well as certain local variables not evaluating in the Locals window. What finally fixed it was enabling the "Suppress JIT optimization on module load (Managed only)" option in the Options->Debug->General tab. Once I set that it was able to bind without issue.