The von Hippel-Lindau (VHL) disease is an inherited tumor susceptibility syndrome featuring a high variety of benign and malignant tumors. The gene has been localized and cloned at 3p25-26. Recent functional analysis defined the VHL gene product as an inhibitor of the transcription elongation process. Its possible involvement in the vascularization process may explain the histologic features of VHL tumors providing insight into basic mechanism of tumorigenesis. Direct genetic testing is available for patients affected with VHL. Seventy to eighty percent of the germline mutations expected could be detected. As first geno/phenotype correlations have been established, we are now beginning to understand the diversity of this fascinating disease at the molecular level. As mutational analysis proved to be of striking prognostic significance, gene testing became an important tool for the management of the disease. The VHL gene was also found to be responsible for tumorigenesis in the corresponding sporadic tumors, especially in the clear cell type of renal cell carcinomas. The understanding of the normal and disturbed function of the VHL gene product will enable us to develop treatment strategies based on and targeted at the molecular cause of the disease. In this review we summarize the current knowledge about genetics, clinics, and function of VHL.