Mounting evidence suggests a role for innate immunity in the early control of HIV infection, before the induction of adaptive immune responses. Among the early innate immune effector cells, dendritic cells (DCs) respond rapidly following infection aimed at arming the immune system, through the recognition of viral products via pattern recognition receptors. This early response results in the potent induction of a cascade of inflammatory cytokines, intimately involved in directly setting up an antiviral state, and indirectly activating other antiviral cells of the innate immune system. However, epidemiologic data strongly support a role for natural killer (NK) cells as critical innate mediators of antiviral control, through the recognition of virally infected cells through a network of receptors called the killer immunoglobulin-like receptors (KIRs). In this review, the early events in innate immune recognition of HIV, focused on defining the biology underlying KIR-mediated NK-cell control of HIV viral replication, are discussed.