<p>Von Hippel-Lindau Syndrome (VHL) is a rare, hereditary disorder characterized by the development of multiple tumors and cysts in various parts of the body due to mutations in the VHL gene on chromosome 3p25-26. Patients with VHL are at increased risk for hemangioblastomas of the brain, spinal cord, and retina, renal cell carcinomas, pheochromocytomas, pancreatic neuroendocrine tumors, and endolymphatic sac tumors. Clinical manifestations vary widely, and early diagnosis through genetic testing and regular surveillance is crucial for effective management. Treatment involves monitoring for tumor development, surgical removal of tumors, and targeted therapies for advanced cases. Recent advances in understanding the VHL pathway have led to new targeted treatments, particularly those involving the hypoxia-inducible factors and vascular endothelial growth factor pathways, which have improved patient outcomes. This article reviews the clinical features, genetic foundations, genotype/phenotype relationship and current management strategies for VHL, emphasizing recent advances that have enhanced prognosis and quality of life for patients.</p>