"Red man syndrome" (RMS) or Red neck syndrome is the most common adverse reaction to vancomycin, characterized by flushing of the upper body, pruritus, mild to profound hypotension, chest pain, and muscle spasm. Rapid intervenous (IV) infusion of vancomycin, a glycopeptide antibiotic, is the most common cause of this syndrome. Even though it is not an allergic reaction, this syndrome most often looks like an Allergy. Some oral drugs, also, release histamine in the body which can result in red man syndrome nevertheless it occurs predominantly during parenteral administration of vancomycin. Discontinuation of the vancomycin infusion and administration of diphenhydramine can be useful to abort most of the symptoms. Slow intravenous administration of vancomycin should minimize the risk of infusion-related adverse effects. Hence Practitioners using vancomycin should be aware of this known drug reaction, its prevention, and treatment.