OBJECTIVE: To describe the pathogenesis of chronic obstructive pulmonary disease (COPD) and mechanisms of benefit, formulations available, drug costs, pharmacokinetic profiles, and pertinent clinical studies for long-acting beta(2)-agonists. DATA SOURCES: A MEDLINE search was conducted from July 1966 through October 2002. STUDY SELECTION AND DATA EXTRACTION: Pertinent articles related to COPD and long-acting beta(2)-agonists. DATA SYNTHESIS: The incidence and subsequent morbidity and mortality of COPD have increased during the last 4 decades, prompting worldwide initiatives to formulate guidelines to decrease the burden of this disease. COPD is a progressive, irreversible disease state characterized by chronic cough, dyspnea, sputum production, and wheezing, in which no medication has been shown to decrease mortality, excluding oxygen supplementation. Bronchodilators have been a mainstay of COPD treatment through their ability to work by both smooth- and non-smooth-muscle mechanisms. Long-acting beta(2)-agonists (i.e., formoterol, salmeterol) dosed twice daily provide more convenient dosing than 4-times-daily regimens of traditional short-acting bronchodilators. Both formoterol and salmeterol have acceptable adverse event profiles when used at recommended doses. There have been no direct clinical outcome studies comparing formoterol and salmeterol, but both have shown some benefits over ipratropiurn and theophylline in improving the symptoms, spirometric indices, exacerbations, and quality of life of patients with COPD. CONCLUSIONS: Based on current evidence, long-acting beta(2)-agonists are acceptable first-line agents for patients with COPD.