von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that is associated with various tumors and cysts in the central nervous system (CNS) and other visceral organs. Inactivation of the VHL tumor suppressor protein with loss of function of the VHL protein, and Elongin B, C complex results in a dysfunction of the ubquitination of hypoxia-inducible factor, which is an important step in the development of highly vascular tumors. The most frequent tumors are hemangioblastoma in the CNS and retina, pheochromocytoma in the adrenal gland, renal cell carcinoma and pancreatic neuroendocrine tumors. In this review, we summarize the recent literatures on the pathogenesis, clinical characteristics, diagnosis and treatment of VHL disease. Progress in molecular diagnosis and molecular targeting therapy is expected to improve the diagnosis and treatment of this disease. Medical, psychological and societal supports for patients with VHL disease and their families and supportive communication among the VHL families are also very important. They have proved to be of benefit for patients with this disease to overcome various social and psychological problems in the US and Europe. Since some drugs targeting the vascular endothelial growth factors or its receptor are undergoing clinical trials, a better prognosis of the tumor in VHL disease can be expected.