Induction of apoptosis is the primary mechanism through which most chemotherapies cause tumor cell death. Early assessment of tumor response is required to manage patients in terms of quality of life versus intensive chemotherapy. Although imaging with radiolabeled annexin V has been intensively investigated, it is still not sufficiently mature for clinical application. This article will summarize various alternative imaging techniques for visualization of phosphatidylserine externalization, activity of caspases, and mitochondrial membrane potential. Such imaging studies will promote the identification of novel molecular targets and the development of highly specific apoptosis-detecting imaging probes with potential clinical applications. It is highly possible that quantitative imaging of apoptosis will greatly improve clinical decision making in apoptosis-related diseases.