Systemic sclerosis or scleroderma (SSc) is a clinically heterogeneous disease of the connective tissue characterised by vascular, immune/inflammatory and fibrotic manifestations. Despite extensive investigations, the key pathogenic links between these disease hallmarks remain obscure, as well as the etiology underlying the beginning of this complex disorder. As for other diseases characterised by prominent autoimmune phenomena, the search for infectious agents responsible for immune tolerance breaks or molecular mimicry events has been a long-pursued issue. In this review, we summarise the current knowledge regarding the association of different viral infections with SSc, focusing mainly on those reports describing a mechanistic interplay between the viral agents and the pathogenesis of SSc. Moreover, we speculate on how viral infections may trigger additional pathogenic mechanisms recently proposed to contributing to SSc phenotype.