This should uninstall anything not in requirements.txt:
pip freeze | grep -v -f requirements.txt - | grep -v '^#' | xargs pip uninstall -y
Although this won’t work quite right with packages installed with -e, i.e. from a git repository or similar. To skip those, just filter out packages starting with the -e flag:
pip freeze | grep -v -f requirements.txt - | grep -v '^#' | grep -v '^-e ' | xargs pip uninstall -y
Then, obviously:
pip install -r requirements.txt
Update for 2016:
You probably don’t really want to actually use the above approach, though. Check out pip-tools and pip-sync which accomplish what you are probably looking to do in a much more robust way.
https://github.com/nvie/pip-tools
Update for May, 2016:
You can now also use pip uninstall -r requirements.txt, however this accomplishes basically the opposite – it uninstalls everything in requirements.txt
Update for May, 2019:
Check out pipenv or Poetry. A lot has happened in the world of package management that makes this sort of question a bit obsolete. I’m actually still quite happily using pip-tools, though.