[6] In 2013, he took a leave of absence from the paper to work on his book Dreamland about the opioid epidemic in America, focusing on abuse of prescription painkillers such as Oxycontin and the spread of Mexican black-tar heroin, primarily by men from the town of Xalisco, Nayarit.

The Atlantic magazine excerpted a portion of The Least of Us titled "'I Don't Know That I Would Even Call It Meth Anymore'" narrating how massive supplies of methamphetamine made in Mexico had spread nationwide and were a major driver of homelessness and mental illness across America.

He wrote in November 2012 about efforts to rework the Mexican indigenous governance system known as usos y costumbres (uses and customs), which has become seen as disadvantaging migrants to the United States and pitting them against people who had remained in their villages.

[10] Writing for the Los Angeles Times in January 2017, Quinones penned an op-ed piece titled, "The Truth is Immigrants have let us live like Princes."

In June 2023, again in the Atlantic, Quinones published a piece insisting that in a time of widespread fentanyl and methamphetamine, law enforcement—and rethinking jail, especially—was essential to compassionately combating the opioid-overdose crisis: "America's Approach to Addiction Has Gone Off the Rails."

In February, 2024, Quinones wrote a piece for The Free Press about Hazard and other towns in Eastern Kentucky using local small-scale enterprise to revive from the damage caused by the opioid epidemic and the departure of coal mines.

[20] In February 2012, Quinones started "True Tales: A Reporter's Blog" about “Los Angeles, Mexico, migrants, culture, drugs, neighborhoods, border, and good storytelling.”[21] Following the release of Dreamland in April 2015, Quinones gave 265 speeches about the book and the opioid epidemic over the next four and a half years to small towns, universities, professional conferences of judges, narcotics officers, doctors, public health and social workers, addiction counselors, and many more.