Severe asthma is characterized by persistent symptoms or recurrent exacerbations despite appropriately delivered high-dose controller therapy, verified adherence, correct inhaler technique, and optimal management of comorbidities and relevant triggers, or by deterioration in control when treatment intensity is reduced. Although severe asthma affects only an estimated 3–10% of patients with asthma, it accounts for the majority of asthma-related morbidity and mortality. Biologic agents constitute an important treatment option for severe asthma, and responses to these therapies vary across endotypes, which are broadly classified as type 2–high or type 2–low. Approved biologic agents for asthma management target immunoglobulin E (IgE), interleukin-5 (IL-5), the interleukin-4 receptor (IL-4R), and thymic stromal lymphopoietin (TSLP). Selection of an appropriate biologic agent is guided by markers of type 2 inflammation, such as blood eosinophil counts, fractional exhaled nitric oxide (FeNO), and serum IgE levels. However, substantial overlap in clinical and inflammatory profiles among patients often complicates identification of the most suitable biologic therapy. This review synthesizes available data from randomized controlled trials and real-world studies evaluating the clinical efficacy of biologic agents in the current management of severe asthma and aims to provide a practical perspective by integrating key biomarkers into clinical decision-making.