Artificial life embraces those human-made systems that possess some of the key properties of natural life. We are specifically interested in artificial systems that serve as models of living systems for the investigation of open questions in biology. First we review some of the artificial life models that have been constructed with biological problems in mind, and classify them by medium (hardware, software, or “wetware”) and by level of organization (molecular, cellular, organismal, or population). We then describe several “grand challenge” open problems in biology that seem especially good candidates to benefit from artificial life studies, including the origin of life and self-organi- zation, cultural evolution, origin and maintenance of sex, shifting balance in evolution, the relation between fitness and adaptedness, the structure of ecosystems, and the nature of mind.