Although the current WHO classification (Swerdlow et al. WHO classification of tumours of haematopoietic and lymphoid tissues. International Agency for Research on Cancer, Lyon, 2008 [1]) for hematolymphoid neoplasms has delineated lymphomas based on the combined morphologic, immunophenotypic, and genotypic findings, further refinement is necessary especially in regard to therapeutics and prognostic implications. High-throughput gene expression profiling (GEP) using microarray technology (Schena et al. Science 270:467-470, 1995 [2]; Augenlicht et al. Proc Natl Acad Sci USA 88:3286-3289, 1991 [3]) was developed about 20 years ago, and further refinement of the technology and analytical approaches has enabled us to routinely evaluate practically the entire transcriptome at a time. GEP has helped to improve the classification and prognostication of non-Hodgkin lymphomas (NHL) as well as improved our understanding of their pathophysiology and response to new therapeutics. In this paper, we will briefly review how this revolutionary tool has transformed our understanding of lymphomas and given us insight into targeted therapeutics. We will also discuss the current efforts in adapting the findings to routine clinical practice, the evolution of the research technology and directions in the future.