DNA methylation is a chemical modification of the bases in genomes. This modification, most frequently found at CpG dinucleotides in eukaryotes, has been identified as having multiple critical functions in broad and diverse species of animals and plants, while mysteriously appears to be lacking from several other well-studied species. DNA methylation has well known and important roles in genome stability and defense, its pattern change highly correlates with gene regulation. Much evidence has linked abnormal DNA methylation to human diseases. Most prominently, aberrant DNA methylation is a common feature of cancer genomes. Elucidating the precise functions of DNA methylation therefore has great biomedical significance. Here we provide an update on large-scale experimental technologies for detecting DNA methylation on a genomic scale. We also discuss new prospect and challenges that computational biologist will face when analyzing DNA methylation data.