End-stage renal disease is a prevalent condition that substantially impacts a patient's quality of life. As medical advancements improve function and rates of survival, the number of persons with end-stage renal disease will grow, with orthopaedic surgeons increasingly encountering patients with the disease in their practice. End-stage renal disease is a complex medical condition that is often associated with multiple medical comorbidities. Orthopaedic surgery in patients with this disease is associated with at least a twofold risk of complications and mortality compared with a population without end-stage renal disease. Patients are at an increased risk for cardiovascular, metabolic, hematologic, and infectious complications. Orthopaedic surgeons should be familiar with pertinent issues in the preoperative evaluation and the postoperative management of these patients and should understand the risks of surgery to better inform patients and family. Careful coordination with consulting specialists is necessary to minimize morbidity and improve outcome.