The pathogenic process of systemic sclerosis targets the skin and internal organs, and involves sequential or concomitant abnormalities in blood vessel function, in immunity and inflammation, and in subsequent fibroblast activation. These characteristics are disease-specific and may partly explain the unresolved therapeutic strategies. These latter must take into account not only the broad biological abnormalities but also the complexities of the disturbances throughout the duration of the disease. However, recent epidemiological data have suggested a decrease in excess mortality, which may be mostly due to the use of cardiovascular drugs. Indeed, the prognoses of the kidney, heart and pulmonary vascular involvements have been improved. Nevertheless and despite several trials, pulmonary fibrosis remains a challenge with no clear efficacy of the regimen of immunosuppressors that have been investigated. This article deals with current and possible future therapeutic options.