Severe or refractory bronchial asthma represents 5-10% of the asthmatic population that responds poorly to high doses of inhaled corticosteroids. Biopharmaceutical approaches have identified new therapies that target key cells and mediators, such as Th2-cells, cytokines, and chemokines. However, some of the clinical trials with these biologics in patients with asthma have been unsuccessful, thus some of these studies had to be discontinued. This article will review current therapeutic strategies of biological immune response modifiers in decreasing pathological immune responses. Therapies using cytokine inhibitors currently provide a way to elucidate the role of individual cytokines in the pathogenesis of human diseases and may yield new approaches to identifying asthma phenotypes.