Though the role of histamine H3Rs as therapeutic target in brain diseases have been the subject of many recent reviews, here we have tried to bring together various neurobiological/neurochemical evidences available so far following H3R ligands in the pathophysiology of AD, ADHD, schizophrenia, and drug abuse each of which is accompanied by deficits of some aspects of cognitive and/or motor functions. Here, HRH3 is linked to Alzheimer disease.