This study aimed to provide a general description of the cardiovascular and hemodynamic effects of dexmedetomidine and an evidence-based review of the literature regarding its use in infants and children with congenital heart disease (CHD). A computerized bibliographic search of the literature on dexmedetomidine use in infants and children with CHD was performed. The cardiovascular effects of dexmedetomidine have been well studied in animal and adult human models. Adverse cardiovascular effects include occasional episodes of bradycardia, with rare reports of sinus pause or cardiac arrest. Both hypotension and hypertension also have been reported. The latter is related to peripheral α(2B) agonism leading to vasoconstriction. No adverse effects on the pulmonary vasculature have been noted even in patients with preexisting pulmonary hypertension. Although there are no direct effects on myocardial function, decreased cardiac output may result from changes in heart rate or increases in afterload. Although not currently Food and Drug Administration (FDA)-approved for the pediatric population, findings have shown dexmedetomidine to be effective in various clinical scenarios of patients with CHD including sedation during mechanical ventilation, prevention of procedure-related anxiety, prevention of emergence delirium and shivering after anesthesia, and treatment of withdrawal. Although dexmedetomidine may have limited utility for painful or invasive procedures, preliminary data suggest that the addition of ketamine to the regimen may offer benefits. When used during the perioperative period, additional benefits include blunting of the sympathetic stress response with a reduction of endogenous catecholamine release, a decrease in intraoperative anesthetic requirements, and a limitation of postoperative opioid requirements.