LegitScript was founded by John Horton, who was a White House aide on drug policy issues from 2002 to 2007. The organization's main office was initially located in Arlington, Virginia but is currently identified as being in Portland, Oregon. The company is identified by the Alliance for Safe Online Pharmacies as a founding member.
In July 2008, LegitScript and KnujOn released a report about 150 websites that offer to sell anabolic steroids over the Internet without requiring a prescription.. This report was also featured in the New York Times, as well as on CNN's Anderson Cooper 360. The report resulted in the termination of large underground steroids rings and controversy at pro-steroids forums. LegitScript and KnujOn also released two reports analyzing Microsoft and Yahoo sponsored search results for Internet pharmacies. Subsequently, Google, Yahoo and Microsoft announced that they were updating their advertising policies related to Internet pharmacies, and would in the future require that Internet pharmacies be approved by the National Association of Boards of Pharmacy's VIPPS program. Shortly thereafter, LegitScript announced that it would be helping Google implement the new policy by monitoring all prescription drug and pharmacy ads for the search engine.
In November 2008, LegitScript reported that it had shutdown 500 "rogue" internet pharmacies by notifying their ISPs and domain registrars. In May 2010, the company released a report regarding over 7,000 displaying a forged pharmacy license, indicating that it worked with 11 different domain name registrars to shut down the websites.
In March 2010, consumer protection website SiteJabber announced that it would begin integrating LegitScript's legitimacy determinations into its Internet pharmacy ratings. In May 2010, the Web of Trust (MyWot) announced a similar initiative in which LegitScript Internet pharmacy legitimacy determinations would be integrated into MyWOT's reputation rankings.
As of September 2010, LegitScript's website indicated that LegitScript had approved over 340 online pharmacy websites as meeting LegitScript's standards, and documented over 47,000 "rogue" online pharmacy websites.