After several decades of debate, it is now widely acknowledged that apoptosis, also known as programmed cell death, is central to homoeostasis and normal development and physiology in all multicellular organisms, including humans. The dysregulation of apoptosis can lead to the destruction of normal tissues in a variety of disorders, including autoimmune and neurodegenerative diseases (too much apoptosis) or the growth of tumors (too little apoptosis). In addition, effective therapy of tumors requires the iatrogenic induction of programmed cell death by radiation, chemotherapy, or both. Given the central role of apoptosis, it would be desirable to have a noninvasive imaging method to serially detect and monitor this process in cancer patients undergoing conventional radiation and chemotherapy treatments as well as for the development and testing of new drugs. In this article, the latest modalities and contrast agents described in the literature for the imaging of apoptosis in vivo are reviewed. First, the most recent developments in the biochemical characterization of the many intracellular pathways involved in this complex process are discussed. Next, a variety of new radionuclide tracers, including radiolabeled annexin V and caspase inhibitors for PET and SPECT, are described. Finally, the use of MRI, MR spectroscopy, and ultrasound as possible alternative imaging modalities for the imaging of apoptosis is addressed.