Apoptosis is an essential physiological process that plays a critical role in development and tissue homeostasis in multicellular organisms, but which is also observed in several eukaryotic microorganisms such as yeast and protozoa. Here, the authors briefly review the most used techniques to detect apoptosis in mammalian cells, especially those that can be applied to parasitic protozoa after different conditions such as drugtreatment. Apoptosis-like processes have been described in protozoa which present mitochondria, such as members of the Kinetoplastida and Apicomplexa groups as well as in protozoa which do not have a mitochondrion, as Entamoeba, Trichomonas and Giardia do. These observations are of interest from an evolutive point of view, especially due to the fact that the participation of the mitochondria in apoptosis has been extensively analyzed in several biological systems. The authors also reviewed the available data showing that several drugs in use as anti-protozoa agents, as well as others which are in the development phase, kill the protozoa through an apoptotic-like process.