Background: The importance of intra-articular corticosteroid treatment for osteoarthritis with its possible adverse effects requires a comprehensive review. Objectives: This review answers the following questions: 1) What evidence is available regarding the symptom-modifying and disease-modifying changes related to a single intra-articular corticosteroid injection for treating osteoarthritis? Moreover, 2) What evidence suggests corticosteroids are detrimental to equine joint health? Study design: Systematic review. Methods: A systematic search was conducted in June/2022 in PubMed, CAB, and the Web of Science. Inclusion criteria were applied to titles and abstracts. For each question, further criteria were applied. The risk of bias was assessed according to the study design. Results: We generated 6,417 titles, and 23 articles fit all inclusion criteria for single-injection corticosteroid treatments; 21 were included regarding corticosteroid effects on joint health. Studies were usually rated as having an unclear risk of bias. Single-injection protocols lead to short-term symptom-modifying osteoarthritic changes with conflicting results regarding disease-modifying osteoarthritis. Healthy joints demonstrated disturbances in metabolism and tissue changes, with dose-dependent effects found in vitro. Main limitations: There is a lack of studies regarding the topics–primarily for equine species. Conclusions: Symptom-modifying osteoarthritic changes after a single injection are short-term; however, a consistent disease-modifying osteoarthritis effect is yet to be established. Joint health appears to be disturbed by corticosteroids as their effects on normal joints show adverse changes in tissues and metabolism.