The term “fibrosis” refers to a spectrum of connective tissue disorders characterized by the excessive accumulation of extracellular matrix leading to organ dysfunction and, ultimately, failure. Fibrosis affects millions of patients worldwide and often manifests itself as a late-stage pathological condition associated with poor prognostic outcome. Although the aetiology and clinical course vary widely depending on the affected organ, fibrotic degeneration of different tissues is underpinned by similar molecular and cellular mechanisms, most notably the persistence and dysregulated activity of myofibroblasts. A systematic search of clinical trials was conducted using PubMed and Cochrane to qualitatively evaluate the effectiveness of different therapeutic approaches to the pharmacological targeting of myofibroblasts in patients affected by fibrotic disorders. The systematic search and screening returned 54 eligible clinical trials, 38 of which reported an improvement of the patients’ symptoms following treatment. The majority of the eligible articles focused on fibrotic degeneration of the respiratory system, skin, liver, and kidneys. The evaluation of clinical data unearthed commonalities between strategies that successfully ameliorated symptoms in patients affected by the same fibrotic disorder. However, none of the treatments evaluated in this study could improve symptoms across a range of fibrotic pathologies. These results indicate that, although no “one size fits all” treatment for fibrosis has yet been identified, the systematic analysis of clinical data can be used to inform the development of therapeutical strategies tailored to suit the diverse aetiology of each fibrotic condition.