In recent years opinions about treatment of systemic sclerosis (SSc) have undergone significant evolution. Currently, drugs which improve microcirculation are considered the treatment of choice in patients with mild disease. The only immunosuppressive drug with confirmed efficacy in reducing cutaneous and pulmonary changes in SSc remains cyclophosphamide. A significant breakthrough was introduction of bosentan as well as an effective, off-label application of mycophenolate mofetil and sildenafil in patients with SSc. Biological therapy with rituximab or other antilymphocyte B recombinant proteins, might develop into the future treatment of systemic sclerosis.