Caffeine, a methylxanthine and nonspecific inhibitor of adenosine receptors, is an example of a drug that has been in use for more than 40 years. It is one of the most commonly prescribed drugs in neonatal medicine. However, until 2006, it had only a few relatively small and short-term studies supporting its use. It is thanks to the efforts of Barbara Schmidt and the Caffeine for Apnea of Prematurity (CAP) Trial Group that we now have high-quality and reliable data not only on short-term but also long-term outcomes of caffeine use for apnea of prematurity. CAP was an international, multicenter, placebo-controlled randomized trial designed to determine whether survival without neurodevelopmental disability at a corrected age of 18 months is improved if apnea of prematurity is managed without methylxanthines in infants at a high risk of apneic attacks. CAP was kept simple and pragmatic in order to allow for maximum generalizability and applicability. Infants with birth weights of 500-1,250 g were enrolled during the first 10 days of life if their clinicians considered them to be candidates for methylxanthine therapy. The most frequent indication for therapy reported in CAP was treatment of documented apnea, followed by the facilitation of the removal of an endotracheal tube. Only about 20% of the neonatologists in the trial started caffeine for the prevention of apnea and the findings of CAP cannot automatically be extrapolated to an exclusive prophylactic indication. However, recent data suggest that the administration of prophylactic methylxanthine by neonatologists is now common practice.