During the last few years, several studies have pointed out the imbalance of immune response with advancing age, which accounts for the increased susceptibility of elderly individuals to life-threatening diseases. This review is focused on the role of neutrophil apoptosis in the age-associated decline of cytotoxicity towards invading micro-organisms. The results indicate that the overall intrinsic mechanisms regulating neutrophil cell death are unaffected by age. Neutrophils from aged humans exhibit a diminished ability to be rescued by proinflammatory mediators, as well as a weak buffer capacity towards proapoptotic reactive oxygen species (ROS) generated during cell stimulation. Such events may hamper in vivo the accumulation of functionally active cells in inflammatory areas, thus contributing to the increased infection-related risk of morbidity and mortality with advanced age. The impact of these new findings in terms of therapeutic applications is discussed.