This article reviews the molecular basis and paradigm shift in the diagnosis and management of skull base tumours. It is now known that the phenotype of meningiomas is influenced by their genotype. Endolymphatic sac tumours are observed in up to 20% of patients with Von Hippel Lindau predisposition syndrome and the tumours express cytokeratin. Schwannomas are distinguished by alterations in NF2 (and mutations in SMARCB1 or LZTR1). Alterations in NAB2-STAT6 fusion influence solitary fibrous tumours, formerly called hemangiopericytomas. Transcription factors like SF-1, T-PIT and PIT-1 help to classify pituitary adenohypophyseal tumours. And identifying genetic drivers of adamantinomatous craniopharyngiomas and papillary craniopharyngiomas as distinct tumours has resulted in developing targeted therapy with BRAF and mitogen-activated protein kinase inhibitors. The review also discusses the molecular basis of chordoma, chondrosarcoma, Langerhans cell histiocytosis and paragangliomas. The authors conclude that understanding the molecular and genetic nature of some skull base tumuors has helped to advance diagnosis, treatment options and prognosis.