Although HAART can reduce HIV-1 viremia to levels below the limit of detection of clinical assays, the virus persists in stable reservoirs, and trace levels of free virions can be found in the plasma. Whether this residual viremia represents ongoing cycles of replication continuing despite HAART or simply the release of virus from stable reservoirs has been controversial. Here we summarize the evidence that HAART can stop ongoing cycles of replication. The evidence comes from a detailed analysis of the residual viremia, which shows it to be archival and non-evolving in character and stable upon intensification of HAART regimens. In addition, new pharmacodynamic measures incorporating a previously ignored slope parameter have provided the first real indication of how well HAART actually suppresses viral replication in vivo. Unexpectedly, some classes of ARVs have highly cooperative dose-response curves that allow as much as a 10-log suppression of viral replication in vivo. Together, these results argue that the ultimate theoretical potential of HAART to control replication of wild-type HIV has already been reached. Applying the same pharmacodynamic principles to the analysis of drug-resistant viruses will allow the rational choice of salvage regimens based on a precise measurement of the inhibitory potential of each drug toward drug-resistant viruses. Progress toward eradication of the infection will require novel approaches to target the stable reservoirs that persist even when viral replication is completely halted.