Chronic obstructive pulmonary disease (COPD) is a common and often progressive inflammatory disease of the airways that is both preventable and treatable. It is well established that those with mild-to-moderate disease severity represent the majority of patients with COPD, yet this subpopulation is relatively under-studied. Because of an insidious pre-clinical phase, COPD is both under-diagnosed and under-treated. Recent studies have confirmed that even patients with mild, grade 1 COPD [i.e. those with a reduced forced expiratory volume in one second (FEV1)/forced vital capacity ratio but normal FEV1], have measurable physiological impairment with increased morbidity and a higher risk of mortality compared with non-smoking healthy controls. Beyond the imperative of smoking cessation-the pivotal intervention in all COPD stages-the role of pharmacotherapy for prevention of disease progression has yet to be established. The main objective of this review is to provide a concise overview of the heterogeneous pathophysiology of COPD with only mild airway obstruction on spirometry and obstacles for early diagnosis. We emphasize that the absence of sufficiently powered trials involving a large number of patients precludes definitive recommendations in support of (or against) long-term pharmacological treatment in mild COPD. Despite these limitations, we present a rationale for earlier pharmacological intervention derived from recent physiological studies performed in symptomatic patients with mild COPD.