Testosterone deficiency is a prevalent condition that frequently affects individuals with end-stage renal disease (ESRD) and those who have undergone renal transplantation. While the etiology of this condition is complex, its implications in this population are far-reaching, impacting various domains such as endocrine profile, sexual and erectile function, bone mineral density (BMD), anemia, and graft survival following renal transplantation. Herein, we review the most recent literature exploring the pathophysiology of testosterone deficiency in ESRD and renal transplant patients, examining its diverse effects on this demographic, and assessing the advantages of testosterone replacement therapy (TRT). Existing evidence suggests that TRT is a safe intervention in ESRD and renal transplant patients, demonstrating improvements across multiple domains. Despite valuable insights from numerous studies, a critical need persists for larger, high-quality prospective studies to comprehensively grasp the nuances of TRT, especially in this vulnerable population. Proactive screening and treatment of testosterone deficiency may prove beneficial, emphasizing the urgency for further research in this area.