The statistics are startling, particularly in light of a multi-year federal, state, and local crackdown on prescription drug abuse.

Each day, at least 40 people in the U.S. die from an overdose of prescription painkillers.

Yet in 2014—the latest figures available from the Centers for Disease Control and Prevention—health care providers wrote 245 million prescriptions for painkillers. That is nearly enough for every American adult to have a bottle of pills.

And the figures come even after several high-profile busts, like the 2010 takedown of Florida brothers Christopher and Jeffrey George, who ran what's believed to be the nation's largest pill mill operation. The business employed corrupt doctors who rubber-stamped prescriptions for thousands of addicts who paraded through their clinics every day. Those clinics dispensed some 20 million pills, meaning the Georges made $40 million in just two years.

The brothers are in prison for a raft of felony counts, including a guilty plea by Jeff George to second-degree murder involving a clinic customer who died from an overdose.

The bust was designed to send a message to those involved in the painkiller trade, says FBI Special Agent Kurt McKenzie, one of the lead investigators in the case.

"You're going to catch heat. There's going to be an investigation. If you're the doctor, you could go to jail. If you're the clinic owner you could go to jail," he tells American Greed.

He says the George case represented an important change in how law enforcement is tackling the issue.

"A standard practice down here had been to address the junkies. Or maybe a doctor from time to time. Nobody had addressed these types of issues as an operation of organized criminal conspiracy, until we got involved and we treated it the way we did," he says.

And yet the problem persists. McKenzie admits that law enforcement can only do so much.

"My opinion is the best solution for this is not just investigative, it is legislative," he says.

"The manufactures are allowed to produce these drugs. They're allowed to distribute these drugs. But the volume and the distribution and the frequency at which these things are prescribed by the physicians on the ground level are the problem too."

Pretty much everyone—including the pharmaceutical industry's main trade group—agrees the most effective tool is a prescription drug monitoring program (PDMP) that can allow law enforcement to track where the painkillers are going and whether they are being overprescribed.

Following a multi-year push, 49 states have established prescription drug monitoring programs. Only Missouri is without one. Legislation there has repeatedly stalled over privacy concerns.

The industry trade group, Pharmaceutical Researchers and Manufacturers of America (PhRMA), says the next step should be making sure the various state programs can talk to one another, sharing information while protecting patient privacy.

McKenzie notes that Florida did not have a PDMP when the George investigation began, but it did by the time it ended.

"That is the biggest tool and best way to curb this problem. It won't make it go away, but it will make it easier for law enforcement to track the activity," he says.

Meantime, the enforcement crackdown is picking up steam.

A four-state sweep last year known as Operation Pilluted resulted in 280 arrests including 22 doctors and pharmacists. The U.S. Drug Enforcement Administration says it was the largest such operation yet.

But just like the bust that took down the George brothers and their massive pill mill in Florida, it won't be the last.

See how the George brothers combined addiction and greed to concoct a prescription for disaster on an ALL NEW American Greed—"Pain Killers Profits"—Thursday July 7 at 10pm ET/PT on CNBC Prime.