Heart failure (HF) is common in the neonatal and pediatric populations. Despite advances in the management of HF, this disease carries significant mortality, morbidity, and socioeconomic burden. The renin-angiotensin-aldosterone system is a therapeutic target in the treatment of HF. In adults, significant advances have been made in the management of HF by targeting the renin-angiotensin-aldosterone system using angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. Only angiotensin-converting enzyme inhibitors have been used in the pediatric population with HF. In this review, we provide an in-depth update on the pathophysiology of HF and discuss the potential future uses of newer and novel pharmacologic interventions in the management of HF in pediatric patients.