Smith, who served as Drugstore.com's initial president, was a director of the company and vice president of strategic partnerships. He plans to start a new entrepreneurial venture, details of which will be released at a later date.
Smith was instrumental in securing Drugstore.com's origininal financing from Kleiner Perkins Caufield & Byers. He also helped develop key partnerships, including those with Amazon.com and Rite Aid. Smith also helped recruit the company's management team.
Drugstore.com said Smith will continue to be an investor in Drugstore.com.
Melinda Gates worked at Microsoft beginning in 1987 and leaving in 1996 as a general manager for product development, after marrying Bill Gates.
Mrs. Gates has focused on philanthropic work in the areas of global health and learning. She is a founder of the William H. Gates Foundation and Gates Learning Foundation. She also focuses on trying to bring computers, Internet access, and training to public libraries in low-income communities through a major library initiative.
Martin Grass, the chief executive of brick-and-mortar pharmacy Rite Aid, has also been appointed a director of drugstore.com.