Genentech (a subsidiary of Roche) and Exelixis are developing cobimetinib, an orally available small molecule, for the treatment of various cancers, including malignant melanoma and breast cancer. Cobimetinib inhibits the MEK (mitogen-activated protein kinase) component of the MAPK/ERK signalling pathway, which is frequently over-activated in human tumours. The product has been approved in Switzerland in combination with vemurafenib for the treatment of patients with unresectable or metastatic BRAF V600 mutation-positive melanoma, and is under regulatory review for the same indication in several countries, including the USA and the EU. This article summarizes the milestones in the development of cobimetinib leading to this first approval for unresectable or metastatic BRAF V600 mutation-positive melanoma melanoma.