Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity and mortality. Therapeutic options are few and are often limited in efficacy. Theophylline is one option, but its use appears to have recently reached a threshold point of deemphasis. Given the consequences of further diminishing the available treatment of COPD, a reappraisal of theophylline's role is imperative. This report reviews the clinical efficacy of theophylline in managing patients with COPD. Special consideration is given to theophylline's effects on pulmonary function (i.e., bronchodilation, exercise capacity, and gas exchange), dyspnea, mucociliary clearance, respiratory muscle performance, cardiovascular function, and neuroinspiratory drive. Despite the lack of standardization in study design and methodology among the studies evaluating theophylline, the conflicting results, and the questions that remain to be answered, evidence indicates that theophylline can provide meaningful therapeutic benefit to patients with COPD. In addition, several studies in patients with COPD have shown that theophylline and inhaled beta-agonists interact in an additive fashion, and the combination therapy results in additional objective and subjective improvement over that achieved by either preparation alone.