The plethora of transporters expressed at the brain barriers all act as selective gatekeepers, and this remains a major obstacle for antiviral therapy. Multi-drug transporters have overlapping substrate specificity for numerous hydrophobic compounds and there seems to be considerable overlap in the efflux transporters used by certain anti-HIV drugs raising the possibility that inhibiting more than one transporter at a time may be one approach to improve CNS delivery of anti-HIV drugs. Although certain studies have demonstrated that simultaneously inhibiting multiple transporters can augment the concentration of anti-HIV drugs in the CNS, this would not appear to be a viable strategy, because it leaves the brain susceptible to damage by putative toxins. However, pharmacological modulation of individual transporters by concomitantly administering HAART with transporter-specific inhibitors may be a more successful alternative to enhance anti-HIV drug levels in the brain, without causing these general and systemic adverse effects (Eilers et al., 2008).