The melanocortin receptors are a subfamily of G-protein-coupled, rhodopsin-like receptors that are rapidly being acknowledged as an extremely promising target for pharmacological intervention in a variety of different inflammatory pathologies, including stroke. Stroke continues to be a leading cause of death worldwide, with risk factors including smoking, diabetes, hypertension and obesity. The pathophysiology of stroke is highly complex: reintroduction of blood flow to the infarcted brain region is paramount in limiting ischaemic damage caused by stroke, yet a concomitant inflammatory response can compound tissue damage. The possibilities of pro-resolving treatments that target this inflammatory response have only recently begun to be explored. This review discusses the endogenous roles of the melanocortin system in reducing characterized aspects of inflammation, and how these, together with potent neuroprotective actions, suggest its potential as a therapeutic target in stroke.