von Hippel-Lindau (VHL) disease is a multisystem inherited cancer syndrome with characteristic tumors and a known genetic basis. Patients with VHL develop, among other tumors, retinal capillary hemangiomas, central nervous system hemangioblastomas, renal clear cell carcinomas, and pheochromocytomas. Nearly all patients can be shown to have a mutation in the VHL gene, which is located on chromosome 3p25. Genetic abnormalities result in abnormal levels of pVHL, which in turn lead to the different tumors. Four distinct phenotypes of VHL disease have been identified based on the relative frequency of and propensity for the development of different VHL tumors. Aggressive screening of patients with VHL disease can prevent morbidity and mortality from these tumors. Although these tumors typically have been treated with observation or surgery, trials of newer medical therapies that target some of the cellular dysregulation caused by mutation in pVHL are ongoing. Even though these trials have not been wholly successful, they present an exciting direction for future research. This article presents a summary of new developments in VHL disease with a focus on ophthalmic and neuro-ophthalmic practice.