Difficult-to-treat asthma is asthma that is uncontrolled despite high intensity treatment. Patients with severe asthma are a subset of this group who remain uncontrolled despite addressing contributory factors, necessitating the use of add-on therapies including biologics. Currently available asthma biologics largely target type 2 inflammatory pathways that drive allergic and eosinophilic asthma. As a proportion of patients may be eligible for more than one biologic, biomarker profile, comorbidities, asthma outcome targets, dosing regimen and costs are important considerations in biologic selection.