Comorbidities associated with obesity have become a worldwide public health concern. Obesity-associated hepatic steatosis is not benign, and the risk of developing severe liver disease is high. Currently, biopsy is the only clinical tool available for the diagnosis of pathological alterations in the liver. However, the procedure is painful and not without risk. As such, there is a need to identify non-invasive biomarkers of steatosis. There has been considerable progress in this area, but research appears to be limited to measurements of levels of certain parameters in patients with liver impairment relative to those of healthy controls. The clinically relevant aim should be to distinguish, at an early stage, those obese individuals with liver steatosis from those obese individuals without it. Plasma constituents that act as surrogates of altered hepatic energy metabolism in response to food intake are likely candidates. Targeted metabolomics, combined with quantitation of the metabolites involved, has been shown to be an efficient measurement tool. Indeed, the evaluation of exhaled volatile compounds might be sufficient, while other rapid, sensitive, and reproducible methods have been validated in preliminary studies in various clinical settings. Metabolomics methods are promising but require considerable expertise and sophisticated (and expensive) equipment not readily available in all centers. The challenge is to adapt this newly acquired, expanding knowledge to current, reasonably equipped clinical laboratories, while substantially reducing costs. Good outcomes are urgently required if effective prevention programs are to be developed to decrease the prevalence of liver disease.