Asthma is a heterogeneous disease, with the immune processes behind the chronic inflammation underlying this disorder differing between the various identified asthma endotypes. In addition to heterogeneity in underlying disease pathophysiology, asthmatics fall across a broad spectrum of disease severity and can vary greatly in their response to convention asthma therapies. A small percentage of patients with severe persistent asthma will remain uncontrolled despite treatment with high-dose inhaled corticosteroids and a long-acting beta-agonist. Less than two decades ago, there were few options for these treatment-refractory asthmatics beyond chronic systemic steroids, with their myriad of treatment-limiting side effects. However, in recent years, there have been a growing number of Food and Drug Administration (FDA)-approved biologic medications with targets that include immunoglobulin E (IgE), interleukin-5 (IL-5), the IL-5 receptor and the IL-4/IL-13 receptor-alpha subunit. The current FDA-approved biologics for severe persistent asthma are omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab. These monoclonal antibodies have been shown to improve asthma control, decrease asthma exacerbations and decrease glucocorticoid dependence in certain subsets of patients with asthma. The optimal biologic for treatment of severe asthma varies from patient to patient, depending on the underlying pathophysiology of the patient's disease. For each of these medications, there are certain biomarkers that can help predict whether a patient is likely to respond favorably to the medication. This review will discuss the currently approved biologics for severe persistent asthma, including their indications, efficacy and side effects.