Colon cancer metastasis is a tightly regulated process that requires a cancer cell to express genes that allow progression through various distinct steps. Aberrations in gene expression by cancer cells leads to transformation, growth, angiogenesis, invasion, dissemination and survival in the circulation, attachment in the organ of metastasis, and again invasion, growth, and angiogenesis. In addition to the genotype/phenotype of the tumor cell, for a tumor cell to become a clinically relevant metastasis, it must be able to respond appropriately to the environment. This includes being able to utilize growth factors and blood vessels from the organ of metastasis for the benefit of the tumor mass. Understanding the molecular and biologic mechanisms of colon cancer metastasis will allow the development of rationale therapeutic strategies that are more likely to impact the natural history of this disease than current therapies.