Its web operations were launched on February 24, 1999, and shut down on September 30, 2016[2] after being acquired by Walgreens in March 2011 for $409 million.

This in turn led to its invention of the first inventory information approval system (IIAS) in 2005; it wasn't used in brick-and-mortar retailing until 2006 by Walgreens.

Under a 2006 Internal Revenue Service ruling, IIAS must be installed by every grocery store, discount store, and Internet pharmacy that accepts FSA debit cards by the end of 2007, and by most chain pharmacies by the end of 2008.

On December 27, 2009, Drugstore.com announced plans to acquire Salu Inc., the operator of SkinStore.com, for $36 million.

[7] On July 28, 2016, Walgreens said it would shut down Drugstore.com and Beauty.com at the end of September, 2016, to focus on its own Walgreens.com website.