The role for anticholinergic medications in acute asthma is not well-defined. Thus, the use of therapy with anticholinergics and β2-agonists, either simultaneously or in sequence, has produced positive as well as negative results in trials. Therefore, the current recommendations for the use of these drugs in the emergency department (ED) and hospital management of asthma exacerbations are not precise. This review answers the following question: what level of evidence is available in the literature to support the use of anticholinergic medications in combination with β2-agonists in acute asthma patients? We limited the search on our therapy question to systematic reviews of randomized trials and/or randomized controlled trials not included in the reviews. After an extensive review of the most relevant evidence, the following conclusions may be emphasized. (1) The use of multiple doses of ipratropium bromide are indicated in the ED treatment of children and adults with severe acute asthma. The studies reported a substantial reduction in hospital admissions (30 to 60%; number needed to treat, 5 to 11) and significant differences in lung function favoring the combined treatment. No apparent increase in the occurrence of side effects was observed. (2) The use of single-dose protocols of ipratropium bromide with β2-agonist treatment produced, particularly in children with more severe acute asthma, a modest improvement in pulmonary function without reduction in hospital admissions; in adults, the data showed a similar increase in pulmonary function with an approximately 35% reduction in the hospital admission rate. In patients with mild-to-moderate acute asthma, there is no apparent benefit from adding a single dose of an anticholinergic medication.