Although the majority of hemangiomas of infancy can be expected to follow a benign course, a significant subset may result in serious complications. Recently, hemangiomas of segmental morphology, or those which are large, plaque-like, and patterned in distribution, have been recognized as important markers for potential complications. PHACE syndrome represents the best known example of the variety of problems that can occur in this setting. The PHACE acronym, which stands for posterior fossa brain malformations, segmental cervicofacial hemangiomas, arterial anomalies, cardiac defects and coarctation of the aorta, and eye anomalies, is sometimes referred to as PHACE(S) when ventral developmental defects such as sternal clefting and supraumbilical raphe are present. This article reviews the specific manifestations of PHACE, reflects on pathogenesis, and discusses appropriate work-up and future directions for this complex and fascinating syndrome. We also discuss other complications associated with hemangiomas of segmental morphology, including ulceration, potential visceral involvement, and underlying anomalies related to the lumbosacral location.