Asthma exacerbations significantly impact millions of patients worldwide to pose large disease burdens on affected patients, families, and health-care systems. Although numerous environmental factors cause asthma exacerbations, viral respiratory infections are the principal triggers. Advances in the pathophysiology of asthma have elucidated dysregulated protective immune responses and upregulated inflammation that create susceptibility and risks for exacerbation. Biologics for the treatment of severe asthma reduce rates of exacerbations and identify specific pathways of inflammation that contribute to altered pathophysiology, novel therapeutic targets, and informative biomarkers. Major steps to prevent exacerbations include the identification of molecular pathways whose blockage will prevent asthma attacks safely, predictably, and effectively.