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Improved knowledge and understanding of key aspects of cancer has led to the development of novel cancer therapeutics acting through complex pathways and mode of actions. The success of these novel cancer therapeutics is often difficult to predict using standard response criteria based on anatomic changes. Monitoring response to cancer therapy at molecular level using Positron Emission Tomography (PET) has gained popularity in recent years. PET allows longitudinal assessment of specific biological processes rather than just changes in anatomic changes in tumor size. In this review, we provide an overview on application for PET imaging to monitor cancer therapy with emphases on PET of tumor metabolism, cell proliferation, angiogenesis, hypoxia and receptor dynamics.