I have tried to puzzle out an answer to this question for many months while learning pandas. I use SAS for my day-to-day work and it is great for it\'s out-of-core support.
I know this is an old thread but I think the Blaze library is worth checking out. It's built for these types of situations.
From the docs:
Blaze extends the usability of NumPy and Pandas to distributed and out-of-core computing. Blaze provides an interface similar to that of the NumPy ND-Array or Pandas DataFrame but maps these familiar interfaces onto a variety of other computational engines like Postgres or Spark.
Edit: By the way, it's supported by ContinuumIO and Travis Oliphant, author of NumPy.