Fibrosis is a major cause of morbidity and mortality worldwide. Tissue injury, with chronic inflammation and fibrogenesis, results in disruption of tissue architecture and eventually organ failure. Currently, the therapeutic options for tissue fibrosis are severely limited and organ transplantation is often the only effective treatment for end-stage fibrotic diseases. However, demand for donor organs greatly outstrips supply, and so effective anti-fibrotic treatments are urgently required. In recent years, Galectin-3 has gained prominence as a central regulator of chronic inflammation and fibrogenesis. Tissue fibrosis models in multiple organs have demonstrated that galectin-3 has profound effects on organ fibrogenesis and scarring. In this review we will examine the ways in which galectin-3 regulates these processes through both direct effects on tissue myofibroblasts and also by mediating cross talk between the innate immune system and fibroblast populations in various organs. Additionally, we will discuss how the manipulation of galectin-3 using small molecule inhibitors may have clinical utility in the treatment of patients with a broad range of fibrotic diseases.