Noninvasive in vivo molecular-genetic imaging uses nuclear, magnetic resonance, and optical imaging techniques. Described and discussed are "direct" imaging of specific molecules and pathway activity, "indirect" reporter gene imaging, and "bio-marker" or "surrogate" imaging. Applications of PET- and optical-based reporter imaging are demonstrated, including imaging of oncogenesis in genetic mouse models, endogenous molecular-genetic-biological properties, and response to therapy in animal models of human disease. Molecular imaging studies complement established ex vivo molecular-biological assays that require tissue sampling by providing a spatial as well as temporal dimension to our understanding of oncogenesis, and the progression and treatment of cancer. Molecular imaging studies being performed in experimental animals will be translated to animals in the near future.