The heterogeneity of asthma is illustrated by the significantly different features of pediatric asthma compared to adult asthma. One phenotype of severe asthma in pediatrics includes atopy, lack of reduction in lung function, and absence of gender bias as the main characteristics. Included in the NIH NAEPP EPR-3 are recommendations for the treatment and management of severe pediatric asthma and critical asthma syndrome, such as continuous nebulization treatments, intubation and mechanical ventilation, heliox, and magnesium sulfate. In addition, epinephrine, intravenous immunoglobulin, intravenous montelukast, extracorporeal membrane oxygenation, and many biological modulators currently under investigation are additional current and/or future treatment modalities for the severe pediatric asthmatic. But, perhaps the most important strategy for managing the severe asthmatic is preventative treatment, which can significantly decrease impairment and risk, particularly for severe acute exacerbations requiring emergency care and/or hospitalization. In order for preventative therapy to be successful, several challenges must be met, including selecting the correct therapy for each patient and then ensuring compliance or adherence to a treatment plan. The heterogeneity of asthma renders the former difficult in that not all patients will respond equally to the same treatment; the latter is only helpful if the correct treatment is employed. Strategies to ensure compliance include education of caregivers and patients and their families. As newer medications are introduced, options for individualized or customized medicine increase, and this may pave the way for significant decreases in morbidity and mortality in severe pediatric asthma.