Exacerbations contribute significantly to impaired health status in chronic obstructive pulmonary disease (COPD), but current therapy can prevent these episodes. Immunization against, for example, influenza offers specific prophylaxis for a minority of episodes. Pulmonary rehabilitation reduces hospital attendance, but its effect wanes. Inhaled bronchodilators such as tiotropium produce similar reductions in exacerbation frequency. Database studies show an association between prescription of inhaled corticosteroids and reduced hospitalization in the older population, a finding confirmed by randomized trials in patients with an FEV1 of less than 50% predicted. Three 1-year randomized clinical trials studied the effect of combining a long-acting β-agonist with an inhaled corticosteroids. In these studies, exacerbation frequency was lower with therapy than placebo. Combination therapy had a similar effect to its monocomponents in the trial of inhaled steroids and long-acting β agonists study using salmeterol and fluticasone. However, when patients with more severe COPD (an FEV1 of less than 36% predicted) were studied using a combination of budesonide and formoterol, a clear improvement was seen in the overall exacerbation rate compared with the β-agonist alone. In addition, the time to first exacerbation was increased compared with either drug alone. Health status changes mirrored these effects. In summary, combination therapy can effectively prevent exacerbations in patients with more advanced COPD.