Brain-targeted chemical delivery systems represent a general and systematic method that can provide localized and sustained release for a variety of therapeutic agents including neuropeptides. By using a sequential metabolism approach, they exploit the specific trafficking properties of the blood-brain barrier and provide site-specific or site-enhanced delivery. After a brief description of the design principles, the present article reviews a number of specific delivery examples (zidovudine, ganciclovir, lomustine benzylpenicillin, estradiol, enkephalin, TRH, kyotorphin), together with representative synthetic routes, physicochemical properties, metabolic pathways, and pharmacological data. A reevaluated correlation for more than 60 drugs between previously published in vivo cerebrovascular permeability data and octanol/water partition coefficients is also included since it may be useful in characterizing the properties of the blood-brain barrier, including active transport by P-glycoprotein.