Even after memories fade they may persist latently in the brain. However, there are no clinically applicable methods for reactivating memory traces and promoting memory retrieval. In the brain histamine modulates learning and memory, sleep and wakefulness, feeding, drinking, and neuroendocrine functions. Animal studies demonstrated that histamine H3 receptor inverse agonists enhance histamine release in the brain and promote learning and memory. In particular, the H3 receptor inverse agonists induce recall of forgotten memories-possibly by facilitating reactivation of memory engram cells. Therefore, H3 receptors are a promising targets for treating cognitive dysfunction. While past clinical trials failed to find beneficial effects of H3 receptor inverse agonists on learning and memory, a recent study showed that inverse agonists enhance memory retrieval in a participant-dependent manner. This review describes the brain's histaminergic system and the modulation of learning and memory by histamine.