Apoptosis, or programmed cell death, is an evolutionarily conserved and highly regulated process of nonfunctional cell death. Through this process, the body disposes of unwanted cells by self-destruction: it is our final defense against damaged cells. In the last decades, many of the essential pathways that control this phenomenon have been elucidated. Apoptosis plays an important role in developmental processes, as well as in cellular homeostasis. This process is known to be accelerated or diminished in many pathologic states. Therefore the understanding of apoptotic regulation has significant clinical ramifications. This article reviews the basic understanding of programmed cell death with respect to areas of interest to pediatric surgeons, including: Hirschsprung disease, intestinal atresias, testicular disorders, short bowel syndrome, ischemia-reperfusion injury and pediatric oncology. Pro or antiapoptotic interventions may become a future target for cell and organ protection in patients suffering from these diseases.