The availability of biologic agents for patients with severe asthma has increased dramatically over the last several decades. The absence of direct head-to-head comparative data and relative lack of biomarkers to predict response can make it difficult to choose the right biologic medication for a given patient. Selecting a biologic agent for the pediatric population presents further challenges due to more limited approved biologic agents and fewer clinical trials in children. In addition, the outcome data that are currently available suggest that treatment responses for a given biologic may be different between adult and pediatric patients. To better understand this possible difference in treatment response, this review focuses on the available efficacy data for biologics evaluated in adult and pediatric patients with severe asthma in addition to other considerations when choosing a biologic agent. Finally, this review discusses how asthma phenotypes differ across age groups and their contributions to the responses to biologic treatment across age groups.