Purpose of Review <p>Alagille syndrome (ALGS) is a multisystem disorder with highly variable phenotypic expression, most commonly presenting with cholestatic liver disease but is also commonly associated with congenital heart defects as well as ocular, skeletal, renal and vascular anomalies. The purpose of this review is to provide a clinical overview of ALGS, as well as highlight current and future approaches to management of these patients.</p> Recent Findings <p>A multidisciplinary approach is often required for patients with ALGS depending on the organ systems involved. While the mainstay of treatment for cholestatic liver disease is primarily supportive, a newer class of medications called ileal bile acid transporter inhibitors have shown promise in improving quality of life, event-free survival and may prevent the need for liver transplantation due to unrelenting cholestatic pruritus. In addition, advancements in gene therapy are showing promise in augmenting signaling pathways and present unique opportunities for alternative therapeutic management.</p> Summary <p>Advancements in molecular diagnostics have led to a better understanding of the genetic mutations of patients with ALGS, however the etiology of the heterogeneity of clinical manifestations remains uncertain. While current therapy options offer symptomatic management, ongoing and future research targeting gene therapy and the disruption of signaling pathways has the potential of treating the underlying disease.</p>