The use of long-acting muscarinic antagonists (LAMA) in asthma is supported by their mechanism of action and evidence of drug synergy with inhaled corticosteroids ± long-acting β-agonists. This review discusses the scientific rationale, clinical data, and recommendations for the use of LAMA in the asthma therapeutic strategy. Adding a LAMA to a dual therapy with an inhaled corticosteroid and long-acting β-agonist has been shown to reduce exacerbations, increase asthma control, and improve quality of life, with a good safety profile. In addition, using a single inhaler device containing multiple drugs enhances patients’ adherence to therapy. Some predictive factors of the efficacy of this triple therapy have been suggested in the literature: patients with a history of at least one exacerbation within the past 12 months, male patients, those younger than 65 years, and non-smokers have been reported to have a greater improvement from baseline forced expiratory volume in 1 second (FEV1) compared with patients without these characteristics, while patients with high bronchial hyperresponsiveness and persistent airway limitations (PAL) seem to show better gains in the exacerbation rate. However, eosinophil levels do not seem to predict the efficacy of LAMA. The role and long-term benefits of LAMA combined with biologic therapy in severe asthma remain uncertain, with more clinical data needed.