The rate of entry into and distribution of many drugs in the mammalian brain cannot be explained by the physicochemical characteristics of these drugs taking into account the anatomy of the blood-brain barrier. Rather, specialized mechanisms (carriers) in the central nervous system have been sought after and characterized. These carriers explain the observed pharmacokinetic behavior of many drugs in brain. This review summarizes these data in the context of the blood-brain barrier and focuses on several broad principles and selected examples.