Apoptosis occurs in the nervous system during normal development, but can also be induced by disease or after exogenous insults such as DNA damage. Depending on the magnitude and timing of the stimulus, apoptosis can be sporadic or widespread. Because of the highly ordered structure of the nervous system, immunohistochemical detection approaches provide a wealth of information about the spatiotemporal nature of apoptosis in this tissue. Therefore, immunohistochemistry offers valuable insights into the neuropathology of disease processes and the identification of specific cell populations that are susceptible to apoptosis. In this chapter, we outline standard approaches for the immunohistochemical analysis of apoptosis in the nervous system, with an emphasis on methodology useful for studies involving DNA damage-induced apoptosis.