Infective endocarditis is defined by a focus of infection within the heart. Despite the optimal care, the mortality approaches 30% at 1 year, so the care for this type of patients represents a challenge to improve the result in your care. The challenges in this clinical entity have several aspects such as the diversity of germs that cause endocarditis, and the most important epidemiologically has generated resistance to antimicrobial treatment along with the possibility of apoptosis in their host-germ interaction. The immunogenetic susceptibility to host infection is discussed, which represents a deep area of research. Inflammation, local and systemic, is complex, with the genesis of reactive oxygen species, which are harmful when the antioxidant defenses are exceeded, causing the break in the mitochondrial electron transport chain with the fall in energy genesis, multiple organ failure, and death. Both at the cellular level and in the mitochondria, possible therapeutic targets are also commented.