Injured joint soft tissues, including tendons and ligaments, repair through an inflammatory process, which can result in fibrosis and persistent tissue abnormality, increasing the likelihood of recurrent injury. The aetiology of disease affecting tendons and ligaments is complex and multifactorial, including interplay between the effects of repetitive wear and tear, daily exercise and ageing. This chapter summarises new knowledge on how inflammation contributes to the onset and progression of soft tissue joint disease, highlighting fibroblasts and macrophages as important tissue-resident cell types implicated in sustaining inflammation. Diseased musculoskeletal soft tissues show plasticity in their inflammatory signatures, which change from the early to advanced stages of disease. After exposure to inflammation, tendons and ligaments mount a protective counter-resolution response, evidenced by the identification of pro-resolving receptors in these musculoskeletal tissues. Studies utilising patient-derived cells support that protective resolution responses may become dysregulated in chronically diseased musculoskeletal soft tissues. Therapeutic strategies that boost endogenous tissue-protective resolution responses could help to prevent chronic inflammation and irreversible fibrosis, providing new treatments for patients with soft tissue joint disease.