Short-acting beta-adrenergic receptor agonists have pharmacologically predictable dose-related and potency-related adverse effects, including tachycardia and tremor, and they also affect serum potassium and glucose. These effects all show tolerance with continued exposure. The potential for arrhythmia is increased by comorbidity and hypoxemia. Nonpharmacologically predictable effects include airway hyperresponsiveness to nonspecific and specific stimuli, including allergen and exercise, and increased airway inflammation. Genetic variants of the beta-adrenergic receptor alter susceptibility to adverse effects of beta-agonists on airway function. The impact of the enantiomers of beta-agonists on adverse effects remains unclear. The two epidemics of asthma death among young people were temporally associated with introduction of potent short-acting beta-agonists (isoproterenol and fenoterol) and appear to be related to adverse effects of these drugs on airway function and airway hyperresponsiveness rather than to cardiotoxicity. Compared with short-acting agents, long-acting beta-agonists show similar but less pronounced pharmacologically predictable effects, and they have not been shown to increase airway hyperresponsiveness in adults. Postmarketing surveillance studies have not suggested significant adverse effects of long-acting beta-agonists on morbidity and mortality.