Progesterone hypersensitivity (PH) is a rare hypersensitivity reaction to either endogenous or exogenous progesterone. There are around 200 reported cases of progesterone hypersensitivity in the medical literature. We present the case of a 31-year-old female who presented with cyclical urticaria and angioedema after exogenous progesterone exposure. Her symptoms would begin a few days before her menstrual cycle began and resolve after menstruation. She only had partial recovery of her symptoms with antihistamines, steroids, montelukast, and omalizumab. She needed treatment with oral contraceptives and had a resolution of symptoms, but subsequently developed a recurrence again. Given the rarity of this condition, the diagnosis is often delayed. This diagnosis should be considered for women of reproductive age who present with cyclic hypersensitivity or allergic symptoms.