Computation is playing an ever increasing and vital role in biology creating demand for new machines. Vendors strive to meet demands with advanced computer architectures such as IBM’s Blue Gene machine. In this talk, I will give a brief overview of the Blue Gene, architecture. I will present some results on a few example problems run on Blue Gene related to computational biology. These examples will give some view of scaling. I will then describe how one might approach using the Blue Gene System in a less traditional way. A challenge to the computational biology community will be to think of “Big” science problems with impact on society that until now or in current implementations have fallen short of the mark. Finally, I will mention opportunities that exist for the community to get access to Blue Gene.