Background: Exercise is not routinely advocated in patients with end-stage renal disease (ESRD) receiving maintenance hemodialysis (HD), compared to best practice in other chronically diseased cohorts. Lack of widespread awareness of the exercise in HD literature may be contributing to these shortcomings of clinical practice. Therefore, our objectives are: (1) to systematically review trials of exercise training involving adult HD patients; (2) to provide empirical evidence that exercise can elicit health-related adaptations in this cohort, and (3) to provide recommendations for future investigations. Method: A systematic review of the literature using computerized databases was performed. Results: According to the 29 trials reviewed, HD patients can safely derive a myriad of health-related adaptations from engaging in appropriately structured exercise regimens involving aerobic and/or resistance training. However, methodological limitations within this body of literature may be partially responsible for minimal advocacy for exercise in this cohort. Conclusions: Robustly designed RCTs with thorough, standardized reporting are required if clinical practice and quality of life of this cohort is to be enhanced through the integration of exercise training and mainstream medical practice. Future trials should demonstrate the clinical importance, and long-term feasibility and applicability of exercise training for this vulnerable patient population.