Siponimod (Mayzent®) is an oral selective sphingosine 1-phosphate receptor subtypes 1 and 5 (S1PR1,5) modulator being developed by Novartis Pharmaceuticals for the treatment of multiple sclerosis (MS) and intracerebral haemorrhage. In March 2019, siponimod received its first global approval in the USA, for the treatment of adults with relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease. Siponimod is under regulatory review in the EU and Japan for secondary progressive MS. This article summarizes the milestone in the development of siponimod leading to this first global approval for MS in the USA.