Colorectal cancer is among the most frequent of human cancers with an estimated 1.4 million new cases of CRC occurred worldwide in 2012. Most colorectal cancers are sporadic, but about 20% of colorectal cancers arise in the context of a familial syndrome or as a complication of inflammatory bowel disease, and these cancers have distinct characteristics. Colorectal cancers develop in different molecular patterns, which are known as the chromosomal instability (CIN), microsatellite instability (MIN) and CpG island methylator phenotype (CIMP) pathways. Results of recent molecular profiling studies have clearly established molecular and genetic heterogeneity of colorectal cancer beyond these established categories, which has resulted in consensus molecular subtypes. About 40% of colorectal cancers are KRAS mutated and these will not respond to EGFR blocking therapies. Microsatellite instable colorectal cancers have gained significant interest recently as they epitomize a category of hypermutating immunogenic tumors, which respond well to immunotherapy through blocking of the PD1 immune-checkpoint.