Non-alcoholic fatty liver disease (NAFLD) is a significant global health burden in children, adolescents and adults with substantial rise in prevalence over the last decades. Accumulating data from manifold studies support the idea of NAFLD as a hepatic manifestation of metabolic syndrome, being rather a systemic metabolic disease than a liver confined pathology. Emerging data support that the gut microbiome represents a significant environmental factor contributing to NAFLD development and progression. Apart from other regimens, probiotics may have a positive role in the management of NAFLD through a plethora of possible mechanisms. The current review focuses on the NAFLD multifactorial pathogenesis, including mainly the role of intestinal microbiome and all relevant issues are raised. Furthermore, the clinical manifestations and appropriate diagnostic approach of the disease are discussed, with all possible therapeutic measures that can be taken, also including the potential beneficial effect of probiotics.