Hypotension represents a very serious clinical problem in patients receiving renal replacement therapy, and it is associated with a significant increase in mortality risk. Infants on chronic peritoneal dialysis (CPD) can be particularly prone to chronic hypotension because of the hyponatremic hypovolemia risk related to their primary renal disease, their nutritional needs, and their peritoneal membrane characteristics. In this setting, if an acute clinical event leads to a further decline in systolic blood pressure, the counteract and perfusion pressure autoregulatory mechanisms can both be impaired, leading to severe complications. Anterior ischemic optic neuropathy (AION) represents an acute ischemic disorder of the optic nerve head and a dramatic cause of sudden blindness, whose incidence is about 1% in children on CPD. In recent studies, very young age, autosomal recessive polycystic kidney disease, and sustained hypotension were found to be substantial risk factors for AON. In infants at risk, strategies of long-term treatment and prevention of peritoneal dialysis-induced hypotension should be applied to prevent progression in the pathophysiologic cascade that leads to chronic hypotension and its complications.