Systemic sclerosis (SSc) is a chronic immune-mediated connective tissue disease with heterogeneous organ involvement. New classification criteria were developed allowing disease identification even before the onset of its hallmark, skin fibrosis. Incidence and prevalence vary among reports and are influenced by methodology. Despite earlier diagnosis, mortality of SSc is still considerable, mainly because of cardiopulmonary causes. Genetic predisposition is entangled and implies genes of the major histocompatibility complex and also other loci related to immune regulation. Known environmental risk factor is exposure to organic solvents and silica, but no single risk factor has emerged. Disease outcome measures including patient-reported outcomes have been proposed and validated, and their use is expected to contribute to measure treatment response in clinical trials. Because of the low frequencies and the high heterogeneity of the disease, large multicenter research collaborations are envisaged to achieve advancement in SSc management.