Nowadays, sepsis is associated with high morbidity and mortality, despite certain achievement has been made in its basic and clinical research. Because of its difficulty in the diagnosis and treatment, it is one of the most common health-threatening diseases. Over the past decade, many studies on septic animals and patients have highlighted immune cell apoptosis in the pathophysiological process of aggravating sepsis. Excessive apoptosis of dendritic cells, macrophages, T lymphocytes and other immune effector cells is the key aspect of immune dysfunction. In addition, accumulated evidence demonstrates that prevention of cell apoptosis can significantly improve the immune status and the survival rate in clinically relevant animal models of sepsis. Therefore, it is quite important to confirm the inducing factors and signaling pathways in the immune cell apoptosis. In this paper, we summarized the role of immune cell apoptosis in pathophysiology of sepsis, and the novel therapeutic strategies based on prevention of apoptosis.