In the drug development process, it remains a difficult task to regulate the entry of the drugs. However, recent progress in studies of the transporter-mediated influx and efflux of endogenous and exogenous compounds, including synthetic drugs, across the blood-brain barrier (BBB) is beginning to provide a rational basis for controlling drug distribution to the brain. This paper describes mechanisms established in the last decade for carrier-mediated influx and efflux of drugs and endocytosis of biologically active peptides across the BBB. The transport systems at the BBB described here are the uptake transporters for nutrients, such as amino acids and hexoses, monocarboxylates, amines, carnitine and glutathione and efflux transporters, such as P-glycoprotein and multiple organic anion transporters. Delivery of cationized peptides across the BBB via adsorptive-mediated endocytosis is also described. By utilizing such highly specific transport mechanisms, it should be possible to establish strategies to regulate the entry of candidate drugs, including peptides, into the brain.