In recent years, significant progress has been made in our understanding of the pathophysiology behind obstructive airway diseases in general and asthma in particular; this knowledge, however, has not translated to major breakthroughs in the treatment of these disorders. Current therapeutic options are less than optimal and frequently are associated with systemic adverse effects. Recent studies indicate that endogenous purine nucleotides, adenosine 5'-triphosphate (ATP) in particular, could play a mechanistic role in obstructive airway diseases through their actions on multiple cell types relevant to these disorders, including mast cells, eosinophils, dendritic cells, and neurons. The pharmacologic modulation of ATP signal transduction in these cells represents an attractive new therapeutic target.