Reported here is a case of rapidly progressive metastatic castration-resistant prostate cancer treated with [177Lu]Lu-PSMA-617 in the setting of severe renal impairment and impending ureteric obstruction. PSMA is expressed on renal tubular cells, raising the possibility of radiation-induced nephrotoxicity, and this level of renal impairment would typically exclude the patient from [177Lu]Lu-PSMA-617 therapy. Multidisciplinary input, individualized dosimetry, and patient-specific dose reduction were used to ensure the cumulative dose to the kidneys remained within acceptable limits. He was initially planned for treatment with six cycles of [177Lu]Lu-PSMA-617. However, he had an excellent response to therapy following four cycles of treatment and the last two cycles were omitted. He has been followed for 1-year posttherapy without evidence of disease recurrence. No acute or chronic nephrotoxicity was observed. This case report highlights the utility of [177Lu]Lu-PSMA-617 therapy in severe renal impairment and provides evidence of relative safety in patients who would otherwise not be considered candidates for therapy.