PubMed search and literature reviews summarized our latest advances regarding the impact of genetic polymorphisms of blood-brain barrier transporters on, and the application of imaging technologies to evaluate and enhance drug delivery to the brain. Although there are reports relating transporter polymorphisms to pharmacokinetics or adverse events, few studies have extended such efforts to the brain. Conceivably, simultaneous nonfunctional expressions of more than one key efflux transporters could result in devastating clinical outcomes if the dose of their substrate drug is not adjusted for the subpopulation with such a phenotype. Imaging technologies have been used to elucidate the kinetic or functional activities of blood-brain barrier transporters, with the majority focusing on P-glycoprotein. Imaging technologies have been used to discover drugs for treating brain disorders, enable targeted delivery in combination with convection-enhanced delivery, assess the therapeutic effect of a treatment protocol and assess drug penetration into brain tumors. Research is limited, however, in using imaging technologies to link the genotype or phenotype of a transporter to the uptake of drug into the brain. No imaging studies have provided clear evidence of transporter polymorphisms discriminating the distribution of drug in the brain. Research efforts are needed to use imaging technologies to explore the correlation between pharmacogenetics and individual clinical outcomes, especially for the phenotype of more than one nonfunctional transporters.