The methylxanthines aminophylline, theophylline and caffeine have been used for more than 30 years to treat apnoea of prematurity. Today, they are among the most commonly prescribed drugs in neonatal medicine. Methylxanthines reduce the frequency of idiopathic apnoea and the need for mechanical ventilation by acting as non-specific inhibitors of adenosine A(1) and A(2a) receptors. However, recent and rapidly growing research into the actions of adenosine and its receptors raises concerns about the safety of methylxanthine therapy in very preterm infants. Possible adverse effects include impaired growth, lack of neuroprotection during acute hypoxic-ischaemic episodes and abnormal behaviour. An international controlled clinical trial is underway to examine the long-term efficacy and safety of methylxanthine therapy in very low birth weight babies.