Although medical treatment of COPD has advanced, nonadherence to medication regimens poses a significant barrier to optimal management. Underuse, overuse, and improper use continue to be the most common causes of poor adherence to therapy. An average of 40%-60% of patients with COPD adheres to the prescribed regimen and only 1 out of 10 patients with a metered dose inhaler performs all essential steps correctly. Adherence to therapy is multifactorial and involves both the patient and the primary care provider. The effect of patient instruction on inhaler adherence and rescue medication utilization in patients with COPD does not seem to parallel the good results reported in patients with asthma. While use of a combined inhaler may facilitate adherence to medications and improve efficacy, pharmacoeconomic factors may influence patient's selection of both the device and the regimen. Patient's health beliefs, experiences, and behaviors play a significant role in adherence to pharmacological therapy. This manuscript reviews important aspects associated with medication adherence in patients with COPD and identifies some predictors of poor adherence.