Cortactin is a cytoskeletal protein and src kinase substrate that is frequently overexpressed in cancer. Animal studies suggest that cortactin overexpression increases tumor aggressiveness, possibly through promotion of tumor invasion and metastasis. Recently, many studies have documented a role for cortactin in promoting cell motility and invasion, including a critical role in invadopodia, actin rich-subcellular protrusions associated with degradation of the extracellular matrix by cancer cells. Here, I review the evidence and potential mechanisms for cortactin as a critical mediator of tumor cell invasion.