Cali Cartel in the context of Miguel Rodríguez Orejuela

The illegal drug trade in Colombia has, since the 1970s, centered successively on four major drug trafficking cartels: Medellín, Cali, Norte del Valle, and North Coast, as well as several bandas criminales, or BACRIMs. The trade eventually created a new social class and influenced several aspects of Colombian culture, economics, and politics.

The Colombian government efforts to reduce the influence of drug-related criminal organizations is one of the origins of the Colombian conflict, an ongoing low-intensity war among rival narcoparamilitary groups, guerrillas and drug cartels fighting each other to increase their influence and against the Colombian government that struggles to stop them.

The Mexican drug war is an ongoing asymmetric armed conflict between the Mexican government and various drug trafficking syndicates. When the Mexican military intervened in 2006, the government's main objective was to reduce drug-related violence. The Mexican government has asserted that its primary focus is on dismantling the cartels and preventing drug trafficking. The conflict has been described as the Mexican theater of the global war on drugs, as led by the United States federal government. Analysts estimate wholesale earnings from illicit drug sales range from $13.6 to $49.4 billion annually.

Although Mexican drug trafficking organizations have existed for decades, their power increased after the demise of the Colombian Cali and Medellín cartels in the 1990s, and the fragmentation of the Guadalajara Cartel in the late 1980s. The conflict formally began with President Felipe Calderón (2006–2012) launching Operation Michoacán in 2006, which deployed tens of thousands of federal troops and police in a militarized campaign against the cartels initially targeted in Michoacán, Ciudad Juárez, Tijuana, and Tamaulipas. However, arrests and killings of cartel leaders caused cartels to splinter into smaller, more violent factions, escalating turf wars and contributing to rising homicide rates nationwide. By the end of Calderón's administration in 2012, the official death toll of the Mexican drug war was at least 60,000. Estimates set the death toll above 120,000 killed by 2013, not counting 27,000 missing.

The Norte del Valle Cartel (Spanish: Cártel del Norte del Valle), or North Valley Cartel, was a drug cartel that operated principally in the north of the Valle del Cauca department of Colombia, most notably the coastal city of Buenaventura. It rose to prominence during the 1990s, after the Cali and Medellín Cartels fragmented, and it was known as one of the most powerful organizations in the illegal drug trade. The drug cartel was led by the brothers Luis Enrique and Javier Antonio Calle Serna, alias "Los Comba", until its takedown in 2008 by the authorities of Colombia and Venezuela, with cooperation of the United States DEA.