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Addendum to: Smirlis D, Duszenko M, Jimenez-Ruiz AJ, Scoulica, E, Bastien P, Fasel N, et al. Targeting essential pathways in trypanosomatids gives insights into protozoan mechanisms of cell death. Parasit Vectors 2010; 3:107; PMID: 21083891; DOI: 10.1186/1756-3305-3-107.Apoptosis is a regulated process of cell death originally described in multicelullar organisms contributing to their development and functionality. There is now increasing experimental evidence that a similar form of cell death is operative in unicellular eukaryotes, including trypanosomatids of the genera Trypanosoma and Leishmania. The determination of ancestral executors and regulators of ‘apoptosis’ in these protozoa belonging to the most primitive eukaryotes that appeared on Earth 1.5 billion years ago, provide an exciting challenge in the understanding of the evolution of apoptosis-regulating processes. A review of the present knowledge of trypanosomatid apoptosis points to the fact that these dying protozoa acquire common apoptotic morphological features as metazoan cells, although they lack many of the molecules accepted today as canonical apoptosis mediators (Bcl-2 family members, caspases, TNFrelated family of receptors). Herein, we discuss how the knowledge of regulators and executors of trypanosomatid apoptosis may provide answers to the gaps concerning the origin of apoptosis. The aim of this addendum is to emphasize the need for classifying the ancestral death program and to discuss how this relates to the complex death programs in multicellular lineages, with the hope to stimulate further enquiry and research into this area.