The classification of the antiretroviral drugs into either low-CNS penetration (rank 0), intermediate CNS penetration (rank 0.5) or high-CNS penetration (rank 1) was based on extensive literature reviews and considered the physico-chemical characteristics of the drug, measured CSF concentrations and effectiveness in the CNS (Table 2) (Letendre et al., 2008a). Drug combinations are ranked by combining the individual drug rankings. However, this simple ranking for drug combinations does not allow for other drug properties, such as drug interactions at the blood–CNS interfaces to be considered, and these factors may actually contribute to lack of, or in fact enhanced, CNS efficacy of specific drug combinations. Recent progress strongly suggests that certain transporters in the BBB impede the access of anti-HIVs to the CNS and that pharmacological modulation of these transporters could be used to our advantage (Eilers et al., 2008).