For all antiretroviral drug classes, drug resistance has been documented in patients failing therapy as well as in therapy-naïve patients infected with transmitted, drug-resistant viruses. Resistance testing is therefore recommended before initiating HAART in therapy-naïve patients as well as when reoptimizing antiretroviral therapy after treatment failure. Given the number of agents and distinct classes of antiretroviral drugs available today, most patients, even those with a history of failure, can be successfully treated. However, as the virus continues to evolve and escape, with even the most effective therapies, new HIV-1 treatments will always be needed.