Coronary microvascular dysfunction has been associated with a wide spectrum of diseases and conditions, and it has proven to be a strong prognostic marker of morbidity and mortality. Despite increased attention guideline-based treatment recommendations are lacking. We performed a systematic review of pharmacological and non-pharmacological interventions to improve coronary perfusion, assessed by intracoronary Doppler, transthoracic Doppler echocardiography, positron emission tomography, cardiac magnetic resonance imaging, transthoracic contrast perfusion echocardiography and dilution techniques. No restrictions were made regarding the study design (randomized, placebo-controlled/ randomized with active comparators/ non-randomized with or without a control group), the cardiac condition studied or the coronary microvascular function at baseline. An electronic database search yielded 4,485 records of which 80 studies met our inclusion criteria. Included studies were sorted according to intervention and study design. Studies were small and heterogeneous in methodology and only few were placebo controlled. Although some treatments looked promising, we found that no specific treatment was sufficiently well-documented to be recommended in any patient groups. There is a need for larger well-designed clinical trials and we suggest that future studies stratify study populations according to pathogenic mechanisms, thereby investigating whether an individualized treatment approach would be more successful. This article is protected by copyright. All rights reserved.