Gene expression profiling in the past 5 years has generated a large amount of data on a variety of malignancies. Unique gene expression signatures have been identified for the more common types of non-Hodgkin lymphoma (NHL), including clinically and biologically important subsets that have not been defined before. In addition, molecularly defined prognosticators have also been constructed for the major types of NHL and these prognosticators provide added value to the widely used International Prognostic Index. The new information should be included in our evaluation of NHL patients, especially when conducting clinical trials. Studies are ongoing to validate and refine these diagnostic and prognostic signatures and to develop platforms that are suitable for routine clinical applications. Similar studies will be performed on the less common types of NHL to complete the molecular classification of NHLs. It is also anticipated that gene expression profiling studies will lead to the identification of novel targets for the development of new therapeutic agents for NHL.