Since the first description in 1961, several case reports have documented an increased incidence of anesthesia-related cardiac arrest in patients with Williams–Beuren syndrome, commonly known as Williams syndrome (WS). Widespread arteriopathy secondary to an elastin gene defect results in various cardiac defects, including supravalvar aortic stenosis (SVAS) and coronary artery anomalies, which can increase the risk of myocardial ischemia. Even though patients with WS are known to have increased risk of adverse events during anesthesia and sedation, they often undergo several procedures that require anesthesia during their lifetimes, and cases of perianesthetic cardiac arrest continue to be reported. To date, no prospective studies have been reported that quantify anesthetic risk in individual patients with WS. In this article, we review the clinical manifestations of WS, propose a consensus, expert-informed method to estimate anesthetic risk based on the current literature, and provide recommendations for periprocedural management of this patient population.