As noted in prior chapters, US national and international guidelines provide a consistent approach to initial management of asthma, based on easily observed physical and physiologic findings, and a detailed history. From those data, a rational initial therapeutic regimen can be prescribed. In many cases, such therapy results in near complete control of asthma symptoms, restoration of normal lung physiology, and elimination of exacerbations. In fact, such improvement is frequent enough that therapeutic responsiveness to asthma treatments was thought to be nearly universal. However, it is not uncommon for patients to return with incomplete, or even trivial improvement in these clinical metrics of control (Langmack and Martin Curr Opin Pulm Med 16:13-18, 2010). In this chapter, we review the current literature on the variability of response to commonly used therapeutic agents in asthma.