Tiotropium bromide is a long-acting, once-daily inhaled anticholinergic approved for the treatment of chronic obstructive pulmonary disease (COPD). Functional and kinetic selectivity for muscarinic (M) receptors, M(1) and M(3), in the lung permit sustained bronchodilation in moderate and severe COPD. Tiotropium is associated with increased lung function, health-related quality of life and exercise tolerance, and reduced dyspnea and acute exacerbations of COPD. It has been hypothesized that tiotropium may retard the accelerated decline in lung function associated with COPD, although a recent study does not support this notion. Tiotropium is safe and well-tolerated, with few side effects. Concerns about cardiovascular side effects and increased stroke risk have been alleviated by a recent, large, multicenter, prospective, randomized trial. Herein, we discuss the pharmacology, physiology and safety profile of tiotropium, as well as the clinical studies that have demonstrated its efficacy in COPD. Additional review of airway muscarinic receptor physiology and cholinergic pathobiology relevant to COPD and asthma provides context for future experimental and therapeutic roles for tiotropium.