The impact of chronic obstructive pulmonary disease (COPD) exacerbations on decline in FEV(1) has been a controversial topic for decades. We will review some of the key studies in this area and discuss potential contributors to inconsistent results of these studies. Dissecting the heterogeneous COPD syndrome into meaningful subtypes and assessing the genetic and environmental influences on COPD-related phenotypes such as exacerbation frequency could clarify the impact of exacerbations on the natural history of COPD.