Functional genomics methods promise a previously unparalleled high-throughput examination of intrahepatic gene expression. Profiling transcriptomes as well as examining the coordinate expression of many genes in diverse pathobiologic pathways is now pssible with techniques such as gene array analysis. However, the nature of the hepatic transcriptome, limitations of the functional genomics methokologies used, and analysis of the data generated are often poorly understood. Further, the use of replicates during analysis and the downstream confirmation of results using a supplemental methokology are important but frequently neglected aspects of experimenta design. This review presents an overview of functional genomics methodoogies in the organ-specific context of studying intrahepatic gene expression. The focus of the review is the most widely used functional genomic methodology, gene array analysis. The nature of the hepatic transcriptome is discussed, together with a summary of gene array analysis methodologies. Analysis of data generated by gene array analysis, determination of intrahepatic cellular origin of transcript expression, and studies of intrahepatic gene expression using gene array analysis are also reviewed. Finally, the importance of a coordinate experimental approach examining both liver protein and mRNA expression is presented. (HEPATOLOGY 2002;36: 1313-1325).