Trypanosoma cruzi is an intracellular parasite, which causes Chagas disease, affecting millions of people throughout the world. T. cruzi can invade several cell types, among which macrophages and cardiomyocytes stand out. Chagas disease goes through two stages: acute and chronic. If it becomes chronic, its most severe form is the chagasic chronic cardiomyopathy, which accounts for most of the fatalities due to this disease. For parasites to persist for long enough in cells, they should evade several host immune responses, one of these being apoptosis. Apoptosis is a type of programmed cell death described as a well-ordered and silent collection of steps that inevitably lead cells to a noninflammatory death. Cells respond to infection by initiating their own death to combat the infection. As a result, several intracellular microorganisms have developed different strategies to overcome host cell apoptosis and persist inside cells. It has been shown that T. cruzi has the ability to inhibit host cells apoptosis and can also induce apoptosis of cells that combat the parasite such as cytotoxic T cells. The aim of this chapter is to present up-to-date information about the molecules and mechanisms engaged by T. cruzi to achieve this goal and how the modulation of apoptosis by T. cruzi reflects in the development of chronic chagasic cardiomyopathy.