Systemic mastocytosis (SM) is a rare disorder with important perioperative implications. The physiological stress of operative procedures and a variety of anesthetic and analgesic medications can be triggers of acute exacerbation of this condition. We present two patients with systemic mastocytosis. One underwent open left inguinal hernia and umbilical hernia repair and the other laparoscopic ventral hernia repair. The literature for perioperative management of patients with SM is extensively reviewed. Both patients were treated preoperatively with intravenous antihistamines and steroids to minimize SM reactions. The first patient underwent uneventful open left inguinal hernia repair and umbilical hernia repair under spinal anesthesia. The second patient underwent general anesthesia. A composite mesh was used to repair a 9 x 12-cm Swiss cheese incisional hernia at the site of previous surgery. After the administration of neostigmine and glycopyrrolate, she developed a generalized rash without any hemodynamic instability. The patient was treated with intravenous Solu-Medrol and Benadryl and was extubated successfully and had an unremarkable postoperative course. Patients with SM require careful perioperative management for surgery under spinal and general anesthesia. These patients can undergo surgical procedures safely and effectively without compromising the standard of care.