Hypertension has traditionally been regarded as an uncommon diagnosis in childhood and adolescence; however, there is compelling evidence to suggest that its prevalence is on the rise, particularly in those with obesity. As a result, pediatricians increasingly are asked to evaluate and manage patients with elevated blood pressure. An increased emphasis on conducting drug trials in children over the last 15 years has yielded important advances with respect to evidence-based data regarding the efficacy and safety of antihypertensive medications in children and adolescents. Unfortunately, data to definitively guide selection of initial agents is lacking. This article will present guidelines for the appropriate use of antihypertensive medications in the pediatric population, including the rational approach to selecting an appropriate medication with respect to pathophysiology, putative benefit, and likelihood for side effects.