Treating patients with refractory asthma remains an ongoing challenge. Although most patients respond to large doses of systemic corticosteroid, the adverse effects associated with such a treatment limit its general use. Clinicians treating patients with refractory asthma must consider tapering systemic corticosteroid at every opportunity. Recent advances in the understanding of the pathogenesis of refractory asthma and corticosteroid resistance have fueled further study in the mechanisms of these processes and have prompted consideration of new treatment approaches. Unfortunately, most alternative approaches require more rigorous evidence to support their regular use.