Chronic fatigue syndrome (CFS) is complex illness with unknown aetiology. Recent research shows that patients with CFS have marked alterations in microbial flora, including lowered levels of bifidobacteria and small intestinal bacterial overgrowth (SIBO). Research also indicates that CFS patients are under increased oxidative stress, have a type 2 helper cell dominate cytokine profile, frequently report allergies, have altered essential fatty acid (EFA) status and may have malabsorption of certain micronutrients. Lactic acid bacteria (LAB) have the potential to influence the immune system in CFS patients by supporting T helper cell 1 driven cellular immunity and may decrease allergies. In addition LAB are strong antioxidants, may improve EFA status, can enhance absorption of micronutrients by protecting the intestinal epithelial barrier, and have been used to treat SIBO. It is our contention that LAB may have a therapeutic role in the treatment of CFS.