Long-acting beta2-agonist (LABA) and inhaled corticosteroid (ICS) combination therapy is recommended by international treatment guidelines for COPD. The current literature concerning the safety of LABAs and ICS, both as monotherapies and in combination, in patients with COPD is reviewed. Bronchodilators such as LABAs are key treatments for COPD due to their effects on bronchial smooth muscle and airflow limitation. LABAs are well-tolerated in patients with COPD, with a low incidence of reported adverse events (AEs). Most AEs associated with LABA use are due to systemic exposure and include muscle tremor and cardiac effects. Placebo-controlled studies in patients with COPD demonstrate that there is no increase in risk of cardiac AEs with LABA therapy. ICS therapy targets airway inflammation in COPD, and is associated with a reduction in the frequency of COPD exacerbations, and improvements in symptoms, lung function and health status. Localized effects such as oropharyngeal irritation are common with ICS, but are not considered to be serious. Potential ocular effects with ICS therapy in patients with COPD have been identified and require further investigation. Rare, but more serious AEs related to ICS use are the effects on bone and the suppression of endogenous cortisol production; however, the clinical relevance of these effects is unclear. Clinical data indicate that LABA/ICS combination therapy is more effective in COPD than either agent used alone and is not associated with any additional AEs.