How to make pdb recognize that the source has changed between runs?

What do you mean by "rerun the program in pdb?" If you've imported a module, Python won't reread it unless you explicitly ask to do so, i.e. with reload(module). However, reload is far from bulletproof (see xreload for another strategy).

There are plenty of pitfalls in Python code reloading. To more robustly solve your problem, you could wrap pdb with a class that records your breakpoint info to a file on disk, for example, and plays them back on command.

(Sorry, ignore the first version of this answer; it's early and I didn't read your question carefully enough.)

The following mini-module may help. If you import it in your pdb session, then you can use:

pdb> pdbs.r()

at any time to force-reload all non-system modules except main. The code skips that because it throws an ImportError('Cannot re-init internal module main') exception.

# pdbs.py - PDB support

from __future__ import print_function

def r():
    """Reload all non-system modules, to reload stuff on pbd restart. """
    import importlib
    import sys

    # This is likely to be OS-specific
    SYS_PREFIX = '/usr/lib'

    for k, v in list(sys.modules.items()):
        if (
            k == "__main__" or
            k.startswith("pdb") or
            not getattr(v, "__file__", None)
            or v.__file__.startswith(SYS_PREFIX)
        ):
            continue
        print("reloading %s [%s]" % (k, v.__file__), file=sys.stderr)
        importlib.reload(v)