Treatment of children with rheumatic diseases has advanced with novel therapeutics and the use of early aggressive treatment to achieve better long-term functional outcome. Many of the current treatments in pediatric rheumatology are based on studies in adults on medications without U.S. Food and Drug Administration labeling for pediatric use. This is not ideal because the pharmacokinetics (absorption, distribution, metabolism, and elimination) of many medications when used in children vary according to age, somatic growth, sexual maturity, and ontogeny of drug-metabolizing enzymes. Special dosing, administration considerations, and toxicity screening are reviewed for the more commonly used medications. Vaccinations for children on antirheumatic drugs are also discussed. Continued study of the long-term impact of medications and biologic treatments on children is necessary, but given the paucity of children with rheumatic diseases, this will require multicentered trials and collaborations. Lastly, this article reviews recent regulatory and legislative action on pediatric drug testing. Passage of the Pediatric Research Equity Act of 2003, which requires 'testing of pharmaceuticals in children, will facilitate more rational use of drugs in pediatric rheumatic diseases in the future.