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Publisher Summary This chapter provides an understanding of the genetic predisposition, somatic genomic alterations, and environmental influences in the development of colorectal cancer (CRC). The emerging genomic-based technologies promise to personalize and improve healthcare. CRC occurs in all races and all peoples, but the rates vary among people with different racial and ethnic backgrounds. Several inherited genetic syndromes that involve a high risk for CRC have been discovered, which include hereditary nonpolyposis colorectal cancer (HNPCC), familial adenomatous polyposis (FAP), and other rare inherited polyposis syndromes. However, these syndromes taken together account for only 5% or less of all CRC diagnoses. The increasing availability and affordability of genetic/genomic tools will improve the diagnosis, screening, treatment, and monitoring of patients in the future. With broader application of these technologies, genomics will be the mainstay of personalized medical care rather than a private application for the unique patient or family. The application of genomic technologies for the patients with CRC or at risk for CRC is also discussed.