Monoclonal antibodies (mAbs) have significantly revolutionized the therapeutic options available to allergists over the past two decades, encompassing four principal categories: anti-IgE mAbs (e.g., omalizumab), anti-IL5/IL-5R mAbs (e.g., mepolizumab, benralizumab), anti-IL-4R mAbs (e.g., dupilumab), and anti-alarmin mAbs (e.g., tezepelumab). The selection of an appropriate mAb is guided by several factors, including disease severity, associated allergic and/or eosinophilic comorbidities, glucocorticoid dependence, and the presence of a type 2 allergic pattern characterized by specific IgE, eosinophils, and in asthma higher levels of fractional exhaled nitric oxide (FeNO). In accordance with the selected criteria utilized to define therapeutic response, super-responders vary across studies, diseases, and biologics to constitute approximately 25-50% of patients. Conversely, in up to 40% of cases, switching therapies may be warranted due to inadequate or ineffective treatment response, glucocorticoid dependence, adverse effects, non-compliance, or, rarely, the development of anti-drug Abs. Discontinuation of anti-allergic mAbs carries a risk of therapeutic failure. However, this risk can be mitigated in selected and well-controlled patients or through gradual tapering strategies such as extending injection intervals or reducing dosages. Omalizumab, an anti-IgE mAb, can be administered either as monotherapy in cases of food allergy, not as a curative intervention but to reduce the risk of allergic reactions, or in combination with allergen immunotherapy (AIT) to attenuate initial allergic reactions, to accelerate desensitization, and to facilitate the consumption of allergenic foods in cases involving tropho-allergens. Emerging research continues to explore new targets, provide improvements in mAb characteristics, as well as the development of biosimilars and multispecific mAb.