Caffeine and theophylline are effective in the treatment of apnea in the newborn infant. Controlled studies of efficacy and comparative efficacy and studies of toxicity are visibly lacking. Both drugs exert their anti-apneic activity by stimulation of the respiratory center. Both drugs are eliminated from the baby slowly (caffeine even slower than theophylline) and doses should be adjusted accordingly. Neonates excrete caffeine largely unchanged and they methylate theophylline to caffeine significantly. Caffeine seems preferable to theophylline because of its wider therapeutic index, ease of administration (i.e., given once per day), lesser fluctuation in plasma concentration owing to longer half-life, potent central respirogenic effect, and fewer peripheral side effects. Areas of concern and feasible research have been discussed.