Background: Previous reviews have highlighted the benefit of loaded therapeutic exercise in the treatment of tendinopathy. Changes in observable structural outcomes have been suggested as a possible explanation for this response to therapeutic exercise. However, the mechanism for the efficacy of therapeutic exercise remains unclear. Objective: To systematically review the relationship between the observable structural change and clinical outcomes following therapeutic exercise. Data sources: An electronic search of AMED, CiNAHL, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PEDro and SPORTDiscus was undertaken from their inception to June 2012. Study eligibility criteria: Any study design that incorporated observable structural outcomes and clinical outcomes when assessing the effect of therapeutic exercise on participants with tendinopathy. Study appraisal and synthesis methods: Included studies were appraised for risk of bias using the tool developed by the Cochrane Back Review Group. Due to heterogeneity of studies, a qualitative synthesis was undertaken. Results: Twenty articles describing 625 patients were included. Overall, there is a strong evidence to refute any observable structural change as an explanation for the response to therapeutic exercise when treated by eccentric exercise training. Moderate evidence does exist to support the response of heavy-slow resistance training (HSR). Conclusions and implications of key findings: The available literature does not support observable structural change as an explanation for the response of therapeutic exercise except for some support from HSR. Future research should focus on indentifying other explanations including neural, biochemical and myogenic changes.