Theophylline and caffeine are both effective stimulants of the central nervous system for the therapy of neonatal apnea. Both drugs are slowly eliminated from the body, and doses should be adjusted to account for this slow elimination. Interconversion of theophylline and caffeine occurs in the newborn infant, with the methylation of theophylline to caffeine as the probable predominant pathway. Caffeine may offer advantages over theophylline: wider therapeutic index, case of administration, less need for therapeutic drug monitoring, less fluctuation in plasma concentrations, and fewer peripheral effects. A major disadvantage of caffeine is in the lack of a readily available commercial preparation. Both drugs exert many pharmacologic actions that require further evaluation in the newborn infant. Long-term effects of these drugs administered during a critical period in the developing human remains an area of concern.