Immune regulation of cellular activation is a tightly regulated process dictated by a balance of activation and inhibitory signals. Although initially described and characterized on natural killer cells, it has become increasingly apparent that inhibitory receptors are expressed and functional on myeloid cells. These receptors can override signals elicited by activation pathways including cytokine and chemokine receptors, growth factor signaling and more recently innate immune receptor signaling. Inhibitory receptors have key roles in various cellular and pathological processes and are thus potential targets for future therapeutics. In this review, the structure and function of inhibitory receptors will be discussed. Furthermore, utilization of these receptors as pharmacological targets and recent examples of strategies targeting inhibitory receptors will be analyzed.