This review explores the current evidence on benefits and harms of therapeutic 
interventions in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and 
makes recommendations. CFS/ME is a complex, multi-system, chronic medical 
condition whose pathophysiology remains unknown. No established diagnostic tests 
exist nor are any FDA-approved drugs available for treatment. Because of the 
range of symptoms of CFS/ME, treatment approaches vary widely. Studies 
undertaken have heterogeneous designs and are limited by sample size, length of 
follow-up, applicability and methodological quality. The use of rintatolimod and 
rituximab as well as counselling, behavioural and rehabilitation therapy 
programs may be of benefit for CFS/ME, but the evidence of their effectiveness 
is still limited. Similarly, adaptive pacing appears to offer some benefits, but 
the results are debatable: so is the use of nutritional supplements, which may 
be of value to CFS/ME patients with biochemically proven deficiencies. To 
summarize, the recommended treatment strategies should include proper 
administration of nutritional supplements in CFS/ME patients with demonstrated 
deficiencies and personalized pacing programs to relieve symptoms and improve 
performance of daily activities, but a larger randomized controlled trial (RCT) 
evaluation is required to confirm these preliminary observations. At present, no 
firm conclusions can be drawn because the few RCTs undertaken to date have been 
small-scale, with a high risk of bias, and have used different case definitions. 
Further, RCTs are now urgently needed with rigorous experimental designs and 
appropriate data analysis, focusing particularly on the comparison of outcomes 
measures according to clinical presentation, patient characteristics, case 
criteria and degree of disability (i.e. severely ill ME cases or bedridden).