Molecular biology of colorectal cancer is evolving. As our understanding of colorectal carcinogenesis improves, we are learning that besides genetic alterations (mutations and deletions), epigenetic inactivation of tumor suppressor genes is a frequent alteration present in most colon cancers. Epigenetic instability includes de novo hypermethylation of CpG dinucleotide clusters (or “CpG islands”) present in the promoter regions of about 50% of human genes, causing transcriptional silencing and a resultant loss of the growth-inhibitory property of the affected tumor suppressor gene. A subset of colon cancers have been shown to exhibit widespread promoter CpG island methylation, referred to as the CpG island methylator phenotype (CIMP). Although CIMP has been established as a unique epigenetic phenotype in colorectal cancer, the molecular basis of these tumors is still poorly understood. This review summarizes our current understanding of CIMP in colon cancer.