The domain Drugs.com was originally registered by Bonnie Neubeck in 1994. In 1999 at the height of the dotcom boom, Eric MacIver purchased an option to buy the domain from Neubeck. In August 1999, MacIver sold the domain at auction for US$823,666 to Venture Frogs, a startup incubator run by Tony Hsieh and Alfred Lin, best known for their involvement in LinkExchange and later Zappos.com. Venture Frogs sold the drugs.com domain name to a private investor in June 2001, allowing Hsieh & Lin to focus on Zappos.com.
The Drugs.com website was officially launched in September 2001.
In March 2008, Drugs.com announced the release of Mednotes--an online personal medication record application which connected to Google Health (On June 24, 2011 Google announced it was retiring Google Health on January 1, 2012).
In May 2010, U.S. FDA announced a collaboration with Drugs.com to distribute consumer health updates on the Drugs.com website and mobile platform.
In February 2016, comScore stated that Drugs.com was the sixth most popular health network receiving approximately 23 million visitors for the month, while Searchmetrics listed Drugs.com in the top 100 US websites for search visibility.
In April 2017, The Harris Poll listed Drugs.com as the Health Information Website Brand of the Year.