Biological pathways and networks represent an important opportunity for understanding biological systems in both normal and diseased states. The mathematical modeling of very large biological pathways presents serious computational challenges. Current pathway models are relatively small, but as larger systems are tackled, current techniques will no longer be adequate owing to their lack of scalability. Some of the resulting challenges are mathematical. Others arise from the knowledge representation, ambiguity, the qualitative nature the information, and the lack of enough information. This talk will discuss the practical utility of modeling a pathway for pharmaceutical research as well as the larger computational issues inherent in mathematical modeling of pathways. The problems span the gamut from analytical mathematics to numerical analysis to computer science and artificial intelligence.