The Government of Mexico is waging a historic campaign against Drug Trafficking Organizations (DTOs). The conflict is a mosaic of several wars occurring at once. The drug cartels are battling for control of territory to expand their market share, protect their operations, and expand into the United States. Secretary of State Hillary Rodham Clinton has referred to the drug war in Mexico as an insurgency. If Mexico continues to follow this path of destruction, it could become a failed state, creating security challenges for the United States. U.S national security documents state that these Transnational Criminal Organizations (TCO) pose a significant threat to U.S. National Security, with dire implications for public safety, public health, democratic institutions, and economic stability. This paper examines the threat of TCOs to U.S. National Security; describes U.S. and Mexican strategies to combat the problem, including the Department of Defense's current role; and recommends that DoD employ a strategy of cooperation, containment, and interdiction to support the U.S. whole-of-government effort to combat Mexican TCOs.