Patients on maintenance hemodialysis are particularly prone to opportunistic infections because of their increased exposure to antibiotics, frequent vascular access, and altered cellular immunity. This case report discusses a 63-year-old African American patient on maintenance hemodialysis who presented with acute painful swelling of her left knee and fever. She was diagnosed to have septic arthritis, candidemia, and arteriovenous (AV) graft infection caused by Candida albicans. The management included removal of the infected AV graft, intravenous fluconazole, and arthrotomy with lavage. The Candida infection subsided, but the patient continued to have knee swelling because of chronic synovitis. We believe that this is the first case of acute Candida septic arthritis in a patient with end-stage renal disease, where hematogenous spread was proven by positive C. albicans cultures from the blood, AV graft, and synovial fluid.