The development of lupus-related end-stage renal disease (ESRD) confers the highest mortality rates among individuals with lupus. Lupus-related ESRD is also associated with higher morbidity and mortality rates compared with non-lupus ESRD. We review the evidence that persistent lupus activity, hypercoagulability, and continuing immunosuppression may contribute to unfavorable outcomes in dialysis and renal transplantation among lupus patients. Robust epidemiologic studies are needed to develop individualized evidence-based approaches to treating lupus-related ESRD. In the meantime, managing lupus-related ESRD presents a significant challenge for clinicians and requires a team approach involving nephrologists and rheumatologists. Goals of therapy after developing ESRD should include continuing monitoring of lupus activity, minimizing corticosteroid exposure, and choosing the most appropriate renal replacement therapy based on patient's risk profile and quality-of-life considerations.