In the 1990s, numerous double-blind, randomized, placebo-controlled trials revealed that theophylline therapy offered no benefit to inhaled beta2 agonists and systemic corticosteroids in the treatment of patients hospitalized for asthma exacerbations. Routine use of theophylline in patients hospitalized for asthma is no longer advocated due to the potential for serious adverse effects and lack of benefit. However, the question remains whether this drug adds any benefits in critically ill patients who are being admitted to an intensive care unit. Two recent pediatric studies suggest that theophylline therapy may have a role in the management of patients with impending respiratory failure who have failed aggressive treatment with inhaled beta2 agonists, systemic corticosteroids, and inhaled ipratropium. If a patient has failed to respond adequately to high-dose routine therapies, theophylline should be initiated by a clinician who is competent in dosing, monitoring serum concentrations, and assessing factors that modify clearance of this high-risk drug. Further clinical research is needed to verify the value of theophylline in adults and children with severe asthma exacerbations and impending respiratory failure.