Peritoneal dialysis (PD) in infants represents one of the greatest challenges for pediatric nephrologists. Over recent years, positive outcome data described by several multicenter experiences and registry studies have increased the amount of information available to help determine whether to initiate a dialysis program in this high-risk patient population. There is no doubt that the rigorous implementation of strategies aimed at preventing infectious complications may have contributed to reducing the morbidity rate of these patients. However, the complex nature of infants with end-stage renal disease and the presence of multiple comorbidities still represent hallmarks that significantly impact on outcome. Although the rigorous application of improved scientific techniques can still contribute to enhancing PD results in infants, we have to acknowledge that the severity of illness in infants, especially at dialysis initiation, represents an undeniable and nonmodifiable factor.