This new edition provides a comprehensive and authoritative overview of the current state of both preclinical and clinical research on histamine and its receptors. It explores novel investigative approaches, including receptor polymorphisms, genetic linkage analysis, and computational modeling. Additionally, it examines the application of new histaminergic ligands in the treatment of various diseases, such as asthma and atopic dermatitis. Several chapters are dedicated to the role of histamine in regulating homeostatic and behavioral functions, including the sleep-wake cycle, appetite control, alertness, pruritus (itch), and the processes of memory formation and consolidation. This edition also introduces newly added chapters focusing on the roles of histamine and its receptors in the kidneys and eyes, both in physiological and pathological contexts, as well as their involvement in motivational processes.