The series is based on Patrick Radden Keefe's New Yorker article 'The Family That Built an Empire of Pain' and Barry Meier's book Pain Killer: An Empire of Deceit and the Origin of America's Opioid Epidemic.

The Sackler family, the owners of Purdue Pharma depicted in the series, has been described as the 'most evil family in America' and 'the worst drug dealers in history'.

The miniseries was created by Micah Fitzerman-Blue and Noah Harpster, with Harpster also taking on an acting role in the series as Curtis Wright.

Production took place in Toronto, beginning in April 2021 and wrapping in November 2021.

The series was directed by Peter Berg.

On Rotten Tomatoes, only 50% of 54 critics gave the series a positive review, with critics noting it was 'undermined by its stale satirical flourishes, resulting in a tonally confused bit of muckraking'.

A writer for the American Council on Science and Health, a pro-industry group, criticized the series for allegedly unfairly placing blame for the opioid crisis on Purdue Pharma and the Sackler family.

Painkiller covers similar subject matter to the Hulu series Dopesick and the documentary The Crime of the Century, both of which also explore the opioid crisis and Purdue Pharma.