AbstractDNA methylation plays a critical role in the regulation of gene expression. The ability to access the methylation status for a large number of genes or the entire genome should greatly facilitate the understanding of the nature of gene regulation in cells, and epigenetic mechanism of interactions between cells and environment. Microarray and sequencing‐based DNA methylation profiling technologies have been developed to meet this goal. These methods can be categorized into three main classes based on how the methylation status is interrogated: discrimination of bisulfite induced C to T transition; cleavage of genomic DNA by methylation‐sensitive restriction enzymes; and immunoprecipitation with methyl‐binding protein or antibodies against methylated cytosines. With the development of next‐generation sequencing technologies, genome‐wide bisulfite sequencing has become a reality. Either whole‐ or reduced‐genome approaches have been used to get the most comprehensive DNA methylation profiles in organisms of various genome sizes. Copyright © 2009 John Wiley & Sons, Inc.This article is categorized under: Laboratory Methods and Technologies > Genetic/Genomic Methods