Acute exacerbations of COPD can complicate the course of the disease in patients with severe airway obstruction. Reduction of exacerbations is an important clinical outcome in evaluating new therapies in COPD. Combination therapies with long-acting beta-agonists and inhaled corticosteroids have now been approved for use. Three 1-year randomized clinical trials, which studied the effect of combining a long-acting beta2-agonist with an inhaled corticosteroid in COPD, documented that exacerbation frequency was lower with therapy than placebo. Combination therapy had a similar effect to its monocomponents in the trial evaluating salmeterol/fluticasone combination. However, when patients with more severe COPD were studied using a combination of budesonide and formoterol, a clear improvement was seen in the overall exacerbation rates compared with the use of a long-acting beta2-agonist alone.