The psychostimulants methylphenidate, dextroamphetamine, and pemoline are among the most common medications used in child and adolescent psychiatry. Often, these agents are used in combination with other medications. This review summarizes reported drug interactions and assesses both causality and clinical significance. A computerized search was undertaken using MEDLINE (1966 to 1998) to obtain all pertinent reports of adverse events associated with the coadministration of psychostimulants and other drugs. A total of 38 reports involving 25 different drugs from various classes were systematically evaluated along with research studies conducted to specifically assess drug interactions. Methylphenidate appeared to be involved primarily in pharmacokinetic interactions suggestive of cytochrome P450 inhibition while dextroamphetamine and pemoline were more often involved in apparent pharmacodynamic interactions. The published data support the safe use of psychostimulants with most classes of medications with few absolute contraindications.