Sonidegib (Odomzo™) is an orally bioavailable, small molecule, Smoothened (SMO) receptor antagonist that is being developed by Novartis for the treatment of cancer. SMO is a G protein-coupled receptor-like molecule that is essential for the actions of the Hedgehog family of secreted proteins, which play a critical role in the development and homeostasis of many organs and tissues. Oral sonidegib is approved in Switzerland for the treatment of adult patients with advanced basal cell carcinoma (BCC) and in the US and EU for the treatment of adult patients with locally advanced BCC that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy. Submissions to other global authorities are being contemplated or planned. Additionally, phase I/II investigation is being conducted in other malignancies, including multiple myeloma, medulloblastoma, myelofibrosis, ovarian cancer, prostate cancer, breast cancer, chronic myeloid leukaemia, myelodysplastic syndromes, oesophageal cancer and pancreatic cancer. This article summarizes the milestones in the development of sonidegib leading to the first approvals for advanced and locally advanced BCC.