Ten years ago things were pretty bad, and I can see how it could be confusing trying to pick through all of the different options that have risen and fallen over the years.

In 2022, If you're building an application and are looking for a simple answer, just use Poetry; it's similar enough to what you'll be familiar with if coming from other languages (e.g. yarn, cargo, ...). For most usecases you can just lean on Poetry's venv management; you don't need to do more than `poetry shell` or `poetry run` to get access to it. Poetry will create, and for the most part manage, your pyproject.toml file for you.

If you want a bit more flexibility Virtualenv is part of python now (`python -m venv`). If you're on MacOS you can get great venv management with pyenv and pyenv-virtualenv. And for sure, things get more complex if you're building a library. But I think Poetry is a solid place to start.