Sepsis is the leading cause of morbidity and mortality in critically ill patients in many intensive care units. The pathophysiology of organ failure and death in patients with sepsis remain elusive. This review focuses on recent advances in our understanding of the mechanisms of cell death in sepsis, the types of cells that are dying and the consequences on immunity. Extensive apoptotic death results in immune cell depletion and may compromise the ability of the patient to eradicate the primary infection and predispose to secondary nosocomial infections. Peripheral circulating lymphocyte apoptosis is also increased in patients with sepsis and correlates with the severity of the disease. In addition, recent evidence indicates that uptake of apoptotic cells impairs the immune function of surviving cells and contributes to immunosuppression. This new understanding of sepsis may lead to novel therapeutic approaches including pharmacological agents that block apoptosis.