Part one of the documentary focuses on Purdue Pharma and the Sackler family, who collaborated with Food and Drug Administration official Curtis Wright IV to get OxyContin approved for wider use.

Patrick Radden Keefe, Andrew Kolodny, Mark Ross, Anna Lembke, Lynn Webster, Roy Bosley, Barry Meier, Art Van Zee (town physician), Paul Pelletier and Giles Sartin appear in part one.

Joe Rannazzisi (a retired DEA Agent), Jonathan Novak, Sari Horowitz, Scott Higham, Lenny Bernstein, David Lazarus, Nathaniel Yeager, Fred Wyshak, Ed Byrne, Will Kimbell, Alec Burlakoff, Sunrise Lee and Caleb Lainer appear in part two.

According to Scott Higham and other commentators, there is an oligopoly of drug distributors: the three main companies are McKesson Corporation, Cardinal Health, and AmerisourceBergen.

The site's critics' consensus reads: "Difficult, but necessary, The Crime of the Century interrogates the origins of the opioid crisis, raising big questions that will likely leave viewers wondering why something hasn't been done about this sooner.