Introduction Reslizumab treats severe eosinophilic asthma in adults not controlled with medical therapy. This drug is a well-tolerated humanized IgG4 kappa monoclonal antibody binding to IL-5 to reduce eosinophils. We report a case of anaphylaxis secondary to reslizumab. Case Description A 71-year-old female with severe persistent corticosteroid-dependent asthma presented with reslizumab anaphylaxis. She had uncontrolled asthma despite 20-30 mg of daily prednisone, montelukast 10 mg qHS, budesonide/formoterol 160/4.5 mcg, and inhaled tiotropium 2.5 mcg. The patient had an absolute eosinophil count of 800. Reslizumab 234 mg monthly was started. After her first dose, she had increased exercise tolerance and weaned off prednisone. After her second injection, the patient failed to report transient urticaria and palpitations beginning 1 hour after reslizumab completion. She took 50 mg diphenhydramine, and symptoms resolved. With her third injection, the patient developed wheezing, urticaria, morbilliform rash, palpitations, and lip swelling 1 hour after completion. She was treated with epinephrine 0.3 mg, prednisone taper, twice daily famotidine 150 mg, and twice daily loratadine. Symptoms resolved, and reslizumab discontinued. Since then, the patient has tolerated benralizumab with no side effects. Discussion Reslizumab significantly reduces eosinophils and improves lung function (AQLQ score, FEV1) thereby improving asthma control and quality of life. The most commonly reported adverse effects include headache, upper respiratory tract infections, and nasopharyngitis. Reslizumab rarely has been associated with anaphylaxis (0.3%), and it is important to establish safety and efficacy. More information is needed for monitoring morbidity and mortality, as well as consequences of withdrawal of therapy.