The objective of this manuscript was to describe the pathophysiology and the systemic and oral implications of chronic renal failure (CRF), end-stage renal failure (ESRF), and renal replacement therapy (RRT) in children and adolescents. Improvement in treatment modalities of CRF, ESRF, and RRT have resulted in an increase in survival, and better health in children and adolescents with renal failure. Therefore, dentists are expected to encounter an increasing number of patients with renal failure needing oral care. Renal failure leads to a state of intoxication known as uremia, which is associated with extra-renal multi-organ involvement. Oral findings frequently include: (1) excessive plaque accumulation; (2) gingivitis; (3) gingival overgrowth; and (4) enamel hypoplasia. Some cases develop periodontitis. It is hoped that the present review will lead to a better understanding of the systemic and oral abnormalities in children and adolescents with renal failure and provide guidance for their treatment and, ultimately, better treatment outcome.