Fibrosing disorders are characterized by abundant accumulation of extracellular matrix proteins such as collagen in a variety of organs, which results in structural changes and dysfunction of the affected organ. Thus fibrotic diseases are characterized by a high morbidity and mortality and also lead to major socioeconomic costs. Systemic sclerosis (SSc) is a prototypic multi-systemic fibrosing disease, which affects the skin and a variety of internal organs, including the lungs, heart and gastrointestinal tract. Targeted antifibrotic therapies are not yet available for clinical use in SSc. In recent years, canonical Wnt signaling has been profoundly characterized as an important mediator of sustained fibroblast activation in fibrotic diseases. In the present review, we will summarize current research on the canonical Wnt signaling pathway in SSc and discuss translational implications and potential limitations of prolonged Wnt inhibition.