We have recently demonstrated that some neuropeptides act as potent endogenous antiparasitic factors. These molecules kill trypanosomes through complex mechanisms that are difficult to escape by the parasite. Neuropeptides are endocytosed by the parasite, disrupt lysosome integrity, and alter the cellular compartmentalization of glycolytic enzymes. This promotes an energetic metabolism failure that initiates an autophagic-like cell death. The concept of autophagy is new for parasites and was mainly associated with differentiation or stress events. Here, we propose that this form of programmed cell death probably co-evolved with parasite-induced-neuropeptides after host infection, as a survival strategy favoring parasite transmission for a longer time by keeping the host alive.