CNS drug candidates fail approval in over 90% of the cases due to poor targeting, lack of efficacy, and/or unacceptable side effects. In vivo imaging offers a pathway to derisk drug molecules at each stage of development, but more research and development is needed to fully realize this potential. The greatest activity is in the use of target biomarkers, but those for disease mechanism, efficacy, and toxicological effects are under study and urgently needed. Many of the biomarker tracers can later be developed as new diagnostic imaging agents and then used to guide individual molecular therapy. Realization of this goal will require ongoing collaborative research and development among universities, pharmaceutical companies, biotechnology, the contract research organization (CRO) industry, diagnostic companies, and producers and distributors of radiopharmaceuticals. During the past decade there has been a progressive merger of the interests of the pharmaceutical industry and academia in the area of molecular biomarker imaging in human brain disease. Historically, academia has been more focused on disease mechanisms, etiology, diagnosis, and treatment monitoring. The pharmaceutical industry has concentrated more on medication development, drug pharmacokinetics, and surrogate treatment end points. In the era of personalized medicine, these interests have evolved to a continuum where the knowledge of diagnosis and molecular mechanism of disease from imaging not only guides new medication development but also is beginning to direct individualized drug choice and dosage.