The local invasion and metastatic spread of tumor cells throughout the body is one of the primary concerns of the oncologist. If all tumors were confined within a defined space, most neoplasms could be removed and subsequently cured with the surgeon’s scalpel. However, this is not the case within the scope of cancer biology. Some neoplasms are highly metastatic (melanoma), while others are rarely metastatic (brain tumors), but given enough time and/or negligence most tumors will spread to distant sites. The intent of this series is to understand the mechanisms that tumor cells use to invade, disseminate and form viable metastatic colonies as well as discuss potential therapies for metastatic disease. This chapter will address the role of the matrix metalloproteinases (MMPs) and their inhibitors in the process of tumor progression, invasion, and metastasis.