Mechanisms for transfers into and out of the brain across the blood–brain barrier and the need for efflux mechanisms. Passive, non-specific transfers can occur via paracellular and transcellular routes, though the rates for paracellular transfer are small. Specific transcellular transport can be passive or active. In addition to the transfers for well-known substances many others are able to enter at various rates, either because they are sufficiently small and lipid-soluble or because barrier mechanisms are not perfect. Substances which enter even though they shouldn’t or are produced “accidentally” by metabolism cannot be allowed to accumulate within the brain. Thus there must be mechanisms for eliminating them