Antimicrobial agents are among the most frequently prescribed therapeutics in the supportive care of children and adolescents with cancer or following hematopoietic stem cell transplantation. Most of these agents are cleared from the body by elimination of unchanged drug by the kidney and/or metabolism by the liver. Impaired renal and hepatic function may have profound effects on the pharmacokinetics and pharmacodynamics of antimicrobial agents, necessitating modification of the dosage regimen in order to avoid toxicity through accumulation of the parent and/or its metabolites. Key to minimize such toxicities is a thorough understanding of the antimicrobial drug armamentarium and a careful evaluation of benefits and risks of antimicrobial interventions. This article reviews the mechanisms of renal and hepatic drug clearance in the normal state and in the state of functional impairment, their implications for antimicrobial therapy and dosage recommendations for pediatric cancer patients with impaired renal or hepatic function.