The histamine system regulates a variety of physiological functions, such as secretion of hydrochloric acid, neurotransmission and immunomodulation. In its core, the histamine system includes four subtypes of histamine receptors and its isoforms by which histamine, an endogenous biogenic amine, carries out its biological effects. The aim of this master’s thesis was to describe the role of histamine system in health and illnesses while reviewing most prominent scientific results that led to development of medications which achieve their effects by modulating the function of the system. During the last few decades great progress has been made in understanding the role of histamine system in many pathophysiological processes, from ulcer and allergies, to diseases of central nervous system. For many years drugs that block histamine H1- and H2-receptors are successfully used in treatment of common medical conditions, such as allergic reactions and peptic ulcer disease. Additionally, the identification of H3- and H4–receptors opened new areas for research about physiological role of the histamine system and development of new drugs. The potential new generations of H3- and H4-antagonists drugs are the subject of many preclinical researches with aim to establish their effectiveness and security profile as well as the optimization of the physical-chemical and pharmacological performance. In clinical studies, most promising compounds are examined for their therapeutic validity for wide variety of conditions such as narcolepsy, cognitive disorders, obesity, schizophrenia, pain and addiction.