Although medical requirements are urgent, no effective intervention has been proven for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). To facilitate the development of new therapeutics, the authors systematically reviewed the randomized controlled trials (RCTs) for CFS/ME to date (1). RCTs targeting CFS/ME were surveyed using two electronic databases, PubMed and the Cochrane library, through April 2019. The results showed that among 513 potentially relevant articles, 55 RCTs met inclusion criteria; these included 25 RCTs of 22 different pharmacological interventions, 28 RCTs of 18 non-pharmacological interventions and 2 RCTs of combined interventions. Eight interventions showed statistical significance: 3 pharmacological (Staphypan Berna, Poly(I):poly(C12U) and CoQ10 + NADH) and 5 non-pharmacological therapies (cognitive-behavior-therapy-related treatments, graded-exercise-related therapies, rehabilitation, acupuncture and abdominal tuina). However, there was no definitely effective intervention with coherence and reproducibility. The authors conclude that this systematic review integrates the comprehensive features of previous RCTs for CFS/ME and reflects on their limitations and perspectives in the process of developing new interventions.