Severe asthma is defined as asthma which requires treatment with high dose ICS plus a second controller and/or systemic corticosteroids to prevent it from becoming “uncontrolled” or that remains “uncontrolled” despite this therapy. In light of the substantial heterogeneity of asthma, this module reviews pharmacologic approaches to optimize treatment of poorly controlled asthma on a personalized basis. This module introduces the various clinical and molecular phenotypes, how this information may be used to inform treatment, and identifies when it may be appropriate to refer to a specialist for management of severe asthma.