The noninvasive detection of apoptosis, or programmed cell death, is an important biomarker for the severity/progression of diseases and the efficacy of anticancer therapies. In the past decade a rapid expansion in the number of apoptosis imaging agents and techniques offers an increasingly wide selection of approaches for the assessment of apoptosis in vivo. The goal of this review is to provide a general account of existing and emerging apoptosis imaging techniques based on their modes of actions; and to critically discuss the major advantages and obstacles facing the field of apoptosis imaging. In conclusion, tremendous progress has been made in applying the concept of apoptosis imaging toward diagnostic needs. However, for imaging strategies involving exogenous agents, we must recognize the intrinsic distinction between probe density and target density, and appreciate the complexity of apoptosis imaging within the context of probe behaviors in the target tissue. For non-pharmaceutical imaging strategies, there is a continued drive to improve the specificity and applicability of these endogenous markers. Overall, what remains to be addressed, and is critical to clinical translation, is the noninvasive quantification, in addition to detection, of apoptosis in vivo.