The widespread use of caffeine-containing beverages has focused research on the mechanisms underlying the central effects of caffeine. 1–3 While the effects of moderate doses of caffeine on behavior are complex, it appears likely that blockades at A1- and A2A-adenosine receptors are the primary molecular sites of action for caffeine. There are at least four types of adenosine receptors in brain. 4,5 The A1-class can be inhibitory to adenylate cyclase, stimulatory to potassium channels, inhibitory to calcium channels, and stimulatory to phosphoinositide breakdown. Selective agonists and selective xanthine and nonxanthine antagonists are available for A1- receptors. The A2A- and A2B-subclasses are stimulatory to adenylate cyclase. The A1- and A2B-receptors differ in affinity and in agonist selectivity. Selective agonists and antagonists for A2A-receptors are available. Selective agents for A2B-receptors are not available. Caffeine is nearly equipotent as an antagonist at A1-, A2A-, and A2B-receptors. The A3-adenosine receptor also occurs in brain, is inhibitory to adenylate 2cyclase, and is remarkable in being insensitive to blockade by caffeine and other xanthines, at least in rodents.