Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are examples of complex diseases accompanied by changes in the expression of thousands of genes and a plethora of proteins encoded by these genes. Before the era of high-throughput analysis, typical translational research initiatives, aimed at defining the molecular targets for complex diseases, were performed on gene-by-gene basis. Innovative technologies, such as expression microarrays, mass spectromety, and reverse proteomics, now allow investigators to reveal complex patterns of the expression of biologically active molecules. For this reason, high-throughput approaches may be well suited for studies designed to untangle the molecular basis of the chronic liver diseases such as NAFLD.