BACKGROUND: Novel therapies targeted to specific tumor pathways are entering the clinic. The need for in vivo monitoring of resulting molecular changes, particularly with respect to the tumor microenvironment, is growing. Molecular imaging is evolving to include a variety of imaging methods to enable in vivo monitoring of cellular and molecular processes. OBJECTIVES: This article reviews the emerging role of molecular imaging in the development of improved therapeutic strategies that provide better patient selection for therapeutic personalization (i.e. determine which therapies have the greatest chance of success given the individual patient's disease genetic, and phenotypical profile). METHODS: In order to illustrate the utility of integrating molecular imaging into therapy development strategies, current and emerging applications of nuclear molecular imaging strategies will be compared with conventional strategies. Proposed methods of integrating molecular imaging techniques into cancer therapeutic development and limitations of these techniques will be discussed. RESULTS/CONCLUSION: Molecular imaging provides a variety of new tools to accelerate the development of cancer therapies. The recent drive to develop molecular imaging probes and standardize molecular imaging techniques is creating the scaffolding for the evolving paradigm shift to personalized cancer therapy.