Living with a chronic illness poses particular challenges, including maintaining current disease knowledge to optimise self-management and interaction with health professionals. People with Multiple Sclerosis (MS) are increasingly encouraged to participate in shared decision making. Making informed decisions is likely to rely on adequate knowledge about the condition and its associated risks. The aim of this systematic review is to explore patients’ existing MS knowledge and MS risk knowledge, and how these relate to demographic and disease variables. A literature search was conducted using PsycINFO, PubMed and Cochrane Library. Eligible studies were published peer-reviewed reporting quantitative measures of MS knowledge and MS risk knowledge in adult MS patients. Eighteen studies met inclusion criteria comprising a total sample of 4,420 patients. A narrative synthesis was undertaken because studies employed various measures. Suboptimal levels of MS knowledge and MS risk knowledge were generally identified across studies. Greater self-reported adherence and a willingness to take medication were related to higher MS knowledge, while educational level was a significant predictor of both MS knowledge and MS risk knowledge. Associations with other demographic and disease-related variables were mixed for both knowledge domains. Direct comparison of results across studies were limited by methodological, sampling and contextual heterogeneity. The review’s findings and implications for future research and clinical practice are considered from this perspective.