Selective serotonin reuptake inhibitors (SSRIs) were introduced in 1987 and, by 1997, were prescribed to 58% of Americans receiving outpatient treatment for depression. In 1992, a study reported that one of the SSRIs, fluoxetine, accelerated the growth of mammary tumors in rodents. By use of data from 1988 to 2002 from their hospital-based, case-control surveillance study, the authors examined the relation between use of SSRIs and risk of breast cancer. Nurse interviewers administered standard questionnaires to patients admitted to hospitals in three US centers to obtain information on demographic, medical, and lifestyle factors and to elicit a history of drug use, including antidepressants. Cases comprised 2,138 women with primary invasive breast cancer, and controls comprised 2,858 women admitted with nonmalignant diagnoses unrelated to SSRI use. The authors used multivariate conditional logistic regression models to estimate odds ratios for breast cancer among regular users of SSRIs compared with nonusers. The odds ratio was 1.1 (95% confidence interval: 0.8, 1.7) for regular use of SSRIs and 0.7 (95% confidence interval: 0.4, 1.5) for use of 4 or more years. Odds ratios were not elevated for any specific SSRI. These data provide some assurance that the use of SSRIs does not increase the risk of breast cancer.