Asthma is at a crossroads. Although the clinical syndrome of asthma has been recognized for millennia, it was research performed in the middle of the last century that established the primary physiologic abnormality as obstruction of the airways to airflow. In addition to airflow obstruction, it was appreciated that the airways of patients were inflamed, that there was hypertrophy and hyperplasia of the mucus secretory apparatus with abnormal amounts of mucus in the airway lumen, and that treatment with adrenergic agonists led to rapid resolution of many of the signs and symptoms of asthma. This latter observation led to the deduction, which still stands, that constriction of the airway smooth muscle was responsible for a substantial proportion of the observed obstruction during an acute asthmatic attack. In the 1970s, as research into the physiology of airflow obstruction reached its peak, investigators began to apply the tools of cell and molecular biology to understanding the root causes of airway obstruction. This resulted in an explosion of new knowledge about the cell and immunobiology of the airway.1 There is now an unprecedented array of potential mechanisms that could lead to the airway obstruction that we recognize as asthma, but there has been little success in sorting out which are the truly active ones. Indeed, it is highly likely that the clinical syndrome of asthma derives from a number of distinct molecular mechanisms. The promise of the future is that the insights derived from the Human Genome Project will provide the keys needed to achieve this distinction at a causal level.