In the recent years, integrase (IN) has emerged as an important new target for the development of anti-HIV-1 agents. The enzyme is involved in a key stage of the retroviral replicative cycle, and interacts with a range of cellular co-factors. Due to the absolute necessity of the enzyme for successful infection and the range of cellular cofactors employed by the enzyme, new ways of targeting both IN and its cofactors could yield agents with improved resistance profiles. Allosteric inhibitors are currently receiving a great deal of focus from both academia and industry alike and offer the possibility of a new class of anti-HIV-1 inhibitor.