Modern methods of gene expression analysis allow the simultaneous characterization of all transcripts, i.e. the entire transcriptome of a cell or tissue. Current DNA microarray-based technologies are able to quantify transcript levels of almost all protein coding genes in the genome. Sequencing-based approaches enable an even more complete investigation, because they provide all sequences of expressed transcripts including previously unknown and non-protein coding RNAs. Cross-sectional studies on gene expression in skeletal muscle, liver, adipose tissue and blood have demonstrated that gene expression profiles in these tissues correlate with insulin resistance and diabetes. Analyses in the population-based KORA survey F4 revealed that mRNA transcripts in whole blood were especially associated with 2 h glucose levels in the oral glucose tolerance test (OGTT). Prospective studies will have to show whether RNA transcripts can help in the early identification of high-risk individuals and in the definition of novel clinically relevant subtypes of type 2 diabetes. Also it remains to be seen whether the combination of biomarkers from different "omics" technologies can give further insight into the development of type 2 diabetes.