Systemic sclerosis (SSc) is a multisystem connective tissue disease characterised clinically by fibrosis and ischaemic atrophy. Internal organ involvement can be life-threatening. Although there are effective treatments for some of the organ-based manifestations of SSc, for example proton-pump inhibitors for upper gastrointestinal disease, no drug has so far been proven to modify the underlying disease process. Our increased understanding of the pathogenesis of SSc, which involves a complex interplay between excessive collagen production, vascular abnormalities and immune dysfunction, is directing development of drugs which hold promise as 'disease-modifying' agents. Some of the drugs under investigation for the treatment of SSc have already been used in other conditions which 'overlap' with SSc, for example primary pulmonary hypertension. Conversely, it is to be hoped that in the future, drugs shown to be effective in SSc might prove beneficial for other fibrotic diseases.