Scientists engaged in drug discovery and development face many critical issues along the road to identifying the best drug candidates to bring forward for testing in patients. In neuroscience, these challenges can involve particularly demanding questions regarding target engagement, the predict ability of endpoints in animal models, new disease model validation, CNS penetration, and the identification of pharmacodynamic markers. For neurological conditions such as Alzheimer's disease, clinical trials of novel drugs that may modify the course of disease, rather than targeting specific symptoms, add extra layers of complexity. Major studies designed to track the course of a disease increasingly depend on noninvasive, translational imaging. In this brief review, we highlight examples of the new wave of neuroimaging studies that engender useful biomarkers of disease for translational research.