The histamine H2 receptor (HRH2), a G protein-coupled receptor, plays a key role in regulating gastric acid secretion, immune responses, and cell proliferation. It is activated by histamine, a biogenic amine involved in physiological and pathological processes. HRH2 antibodies are tools designed to detect, quantify, or modulate HRH2 activity in research and clinical contexts. In research, these antibodies are widely used to study HRH2 expression patterns in tissues, its role in diseases (e.g., cancer, allergies, gastrointestinal disorders), and its interactions with signaling pathways. Clinically, HRH2 antagonists (distinct from antibodies) have long been used to treat acid-related conditions, but HRH2-targeting antibodies are emerging as potential therapeutics, particularly in oncology. Overexpression of HRH2 has been observed in certain cancers, where it may promote tumor growth and immune evasion. Antibodies against HRH2 could block these pro-tumorigenic effects or deliver targeted therapies. Additionally, HRH2 antibodies aid in diagnostic applications, such as identifying HRH2-positive tumors or monitoring receptor expression in inflammatory conditions. Challenges include ensuring antibody specificity and understanding HRH2's dual roles in different cellular contexts. Ongoing studies explore their utility in combination therapies and immune modulation.