The basic science understanding of the pathophysiology of a disease often serves as the basis for clinical investigations. This knowledge is used to propose new directions in care and confirm initial concepts. The basic science of asthma demonstrates that the most comprehensive management of inflammation appears to be associated with the use of inhaled corticosteroids and proposes a mechanism for combination therapy with the addition of salmeterol. Randomized clinical trials are performed to confirm these initial observations and demonstrate both the safety and efficacy of therapeutic agents. These investigations are either placebo-controlled or direct comparisons of 2 medications. For the treatment of asthma, these studies have all consistently demonstrated that inhaled corticosteroids are the most effective primary controller therapy. Greater improvement in both lung function and patient-oriented symptom control is observed with the use of inhaled corticosteroids. For patients whose symptoms are not controlled with single-drug therapy, the addition of a long-acting bronchodilator appears to be the most effective add-on treatment with the greatest improvement in lung function and symptom control. Clinical trials have been used for the purposes of cost modeling. Therapies that produce the greatest effect size at the lowest incremental costs produce the greatest improvement in cost-effectiveness. Retrospective claims analysis, more recently, have been used to validate these observations from clinical trials. These studies measure both resource use and costs or charges. These analyses have confirmed that initial treatment with inhaled corticosteroids and combined treatment with inhaled corticosteroids and long-acting bronchodilators are the most effective stepwise approaches to the treatment of asthma.