The chemokine coreceptor 5 (CCR5) antagonists are antiretroviral agents with an extracellular, host-targeted mechanism of action against HIV. Maraviroc, the first-in-class CCR5 antagonist, received regulatory approval in 2007, becoming the first oral antiretroviral from a new class in more than 10 years. Other compounds in this class are in various stages of clinical development. In 2005, we reviewed the limited clinical data then available on CCR5 antagonists. In this follow-up review, we revisit the field and assess the clinical and virological data that have emerged in the 4 years since, with particular reference to maraviroc for which the most comprehensive data currently exist.