Aims The purpose of this review is to update the current understanding of dimethyl sulfoxide (DMSO) and its role in the treatment of interstitial cystitis (IC). Methods A systematic review was conducted using the PRIMSA checklist to identify published articles involving intravesical DMSO for the treatment of IC. Results Thirteen cohort studies and three randomized‐controlled trials were identified. Response rates relying on subjective measurement scores range from 61 to 95%. No increased efficacy was found with “cocktail” DMSO therapy. Great variation existed in diagnostic criteria, DMSO instillation protocols and response measurements. Conclusions The current evidence backing DMSO is a constellation of cohort studies and a single randomized‐controlled trial versus placebo. The optimal dose, dwell time, type of IC most likely to respond to DMSO, definitions of success/failure and the number of treatments are not universally agreed upon. Improvements in study design, phenotyping patients based on symptoms, as well as the emergence of reliable biomarkers of the disease may better guide the use of DMSO in the future.