Deregulated apoptosis is involved in several diseases including myocardial infarction, ischemia and neurodegenerative disorders, which are characterized by excessive apoptosis. In contrast, resistance to apoptosis is defined as one of the hallmarks of cancer. It therefore follows that strategies that enable the quantitative detection of apoptosis modulation in vivo would be of enormous benefit in the clinic for diagnosis and patient management (evaluation of response to treatment). In addition, such strategies could be used to evaluate the efficacy of novel therapeutics along their development process. During the development of novel therapeutics it would be necessary to evaluate drug efficacy in vitro and then in experimental animal models and, ultimately, in clinical trials. Currently there is no one single probe that is suitable for imaging apoptosis at every stage of evaluation, necessitating a switch between probe types during the development process. This has key implications for the quality and reproducibility of the data obtained. The present review summarizes the development of new apoptosis detecting probes that have the potential for bridging different stages of the evaluation process such that accurate, translational apoptosis imaging data are obtained.