The short- and long-term effects of the widespread use of diethylstilbestrol (DES) over 3 decades have become a distant memory for many clinicians. Others are too young to remember the flurry of activity in the early 1970s on the part of many medical centers to identify the offspring of women who were prescribed DES during their pregnancies. This medication was given in an attempt to prevent multiple pregnancy-related problems such as miscarriage, premature birth, and abnormal bleeding. The recognition of the association of DES with an increased incidence of cervical and vaginal cancers in very young women led the Food and Drug Administration to ban its use during pregnancy in 1971. Other pregnancy-related problems for the daughters and genitourinary tract changes in the sons did not become apparent until years later. Ongoing follow-up of these offspring has raised concerns for their future as well as their mothers' future. Clinicians need to be up-to-date with current knowledge regarding risks for cancer and other health-related issues.