The definition of persistent asthma in longitudinal studies reflects symptoms reported at every assessment with no substantive asymptomatic periods. Early-childhood wheezing may be transient, especially if it is of viral etiology. Longitudinal studies provide greater opportunity to confirm the diagnosis by variability of symptoms, objective measurements, and therapeutic responses. Several clinical phenotypes of childhood asthma have been identified, with general consistency between cohorts. Persistent wheezing is often associated with loss of lung function, which is evident from early-childhood and related to persistent inflammation and airway hyperresponsiveness. Female sex, atopy, airway responsiveness, and personal smoking, but not exposure to environmental tobacco smoke, are risk factors for persistence of childhood asthma into adulthood. The effect of breastfeeding remains controversial, but gene-environment interactions may partly explain outcomes. Understanding the natural history and underlying causes of asthma may lead to development of strategies for primary prevention.