Life at its basics
At its basics, I would like to use the definition of something that can reproduce itself without outside interference. Viruses aren't much more than reproducing molecules, but they fit the definition.
I would guess that over 99% (mass) of Terrestrial organisms use oxygen as part of their energy transfer mechanism. Yet it is fairly common to find sulfur-metabolizing bacteria, and someone told me they found some truly weird organisms near some of the deep-sea heat vents that get their energy from thermal cycling. Given this diversity, is it unrealistic to find life using bizarre, unknown energy cycles out there?
The big problem is going to be how to shoot the breeze with something where the only things you have in kind are that you are alive and intelligent.
