The Division of Precision Medicine at the Martinos Center at MGH focuses on designing, creating, and testing new methods for imaging and therapeutic targeting of important biological pathways in disease. We are driving the next wave of Molecular Imaging to improve patient care through precision medicine. The process spans imaging probe development, creation of appropriate cell-based and animal models of pathology, imaging device development, and the clinical translation of the optimized concepts to help detect disease and therapeutic response in people. Many of the fundamental processes that drive cancers, cardiovascular disease, neurodegeneration, and autoimmune disease are interrelated. Imaging key regulatory pathways and cell types in these processes allows non-invasive assessment to improve early disease detection, evaluation of which pathways are up or down regulated, and determination of the efficacy of molecularly targeted therapy to assess response at an early stage. Our imaging efforts focus on PET, optical-fluorescence, MR, and SPECT imaging in both preclinical systems and in people. Over the years, we have translated a number of imaging agents into humans to better understand pharmacokinetics and pharmacodynamics of therapeutic interventions. We continue to develop preclinical and clinical imaging and theranostic paradigms to improve the efficacy of targeted treatment.