Mastocytosis is a rare disease characterized by the abnormal accumulation of monoclonal mast cells in various organs. In the perioperative period, many triggers may lead to excessive mast cell degranulation and mediators release, which can result in a severe anaphylactoid or anaphylactic response with anaphylactic shock. Patients with mastocytosis are more likely to experience perioperative reactions associated with inflammatory mediator release. The aim of this article is to provide physicians treating patients with mastocytosis and mast cell activation syndrome with practical advice for the management of surgery, childbirth, and radiological examinations and a list of medications with a lower risk of side effects.