For decades anatomic imaging with computed tomography or magnetic resonance imaging has facilitated drug development in medical oncology by providing quantifiable and objective evidence of response to cancer therapy. In recent years metabolic imaging with [18F]fluorodeoxyglucose-positron emission tomography has added an important component to the oncologist's armamentarium for earlier detection of response that is now widely used and appreciated. These modalities along with ultrasound and optical imaging (bioluminescence, fluorescence, near-infrared imaging, multispectral imaging) have become used increasingly in preclinical studies in animal models to document the effects of genetic alterations on cancer progression or metastases, the detection of minimal residual disease, and response to various therapeutics including radiation, chemotherapy, or biologic agents. The field of molecular imaging offers potential to deliver a variety of probes that can image noninvasively drug targets, drug distribution, cancer gene expression, cell surface receptor or oncoprotein levels, and biomarker predictors of prognosis, therapeutic response, or failure. Some applications are best suited to accelerate preclinical anticancer drug development, whereas other technologies may be directly transferable to the clinic. Efforts are underway to apply noninvasive in vivo imaging to specific preclinical or clinical problems to accelerate progress in the field. Because resources are limited, and patient suffering from failed or ineffective therapy continues, a concerted effort is being made to address these issues. Many simultaneous activities involving academia; the pharmaceutical, device, and biotechnology industries; US Food and Drug Administration; National Cancer Institute; Centers for Medicare and Medicaid Services; and specialized networks sponsored by the National Institutes of Health are beginning to address these issues to develop consensus recommendations and progress in this important area.