In order to examine drug interactions at the transporter level of the blood–CNS interfaces in more detail, a clear picture of drug movement into the CNS is clearly warranted. This may prove useful in fine-tuning this ranking scheme and is the focus of this review. We will start with a summary of current anti-HIV drugs and how molecules are restricted from crossing the blood–CNS interfaces. This will then be followed by a brief overview of those membrane transporters considered to be relevant to the disposition and effectiveness of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs) and protease inhibitors (PIs). Possible future research directions will then be discussed.