Both diagnosis and treatment of cancer have changed dramatically in the recent past, as research in animal models and patients has identified the molecular alterations that occur in the initiation and progression of many tumors. This new level of understanding has identified a myriad of targets for potential drugs designed to inhibit specific alterations in tumor cells, provided opportunities to stratify patients according to level of risk, and suggested methods to detect cancer earlier. In parallel, our ability to image functionally the molecular and biochemical changes that occur in tumors has advanced dramatically – both in patients and in animal cancer models. Magnetic resonance imaging (MRI) can identify previously undetectable lesions, positron emission tomography (PET) can utilize changes in tumor biochemistry to locate tumors and monitor their functional characteristics and optical imaging technologies (FRI, FMT) are at the verge of being introduced into clinical care to expand the realm of what the human eye can perceive. These technologies, coupled with other imaging modalities, have altered our ability to detect tumors, stage tumor progression, observe metastases, detect recurrences and rapidly monitor tumor responses (or lack of response) to alternative therapies. The development of small animal MRI and microPET instrumentation, and instrumentation for optical imaging of bio- luminescence and fluorescence, has brought non-invasive molecular imaging into the toolbox of researchers who study cancer in small animal models in which the mice are subject to extensive genetic manipulation.