In the early years of NIDA-supported drug abuse research, much of the research on women was treatment related and conducted out of concern for their pregnancy status. Since then, drug abuse research on women has expanded to include females of all ages, including infants, children, and adolescents, both human and animal. This expansion has also extended to the study of male-female differences. In the early years of the expansion, National Institutes of Health study sections demanded a heavy burden of proof from drug abuse researchers who proposed to study male-female differences. The need for such research appeared not to have face validity. The tide has now changed with the growing body of literature attesting to its scientific and clinical validity. This change is often reflected in concerns expressed in study sections reviewing drug abuse grant applications that an applicant does not propose to analyze the data for sex-gender differences when in fact the literature suggests that such differences would be observed. Although the change has been slow, it suggests that the burden of proof is shifting from having to defend why sex-gender differences should be studied to having to defend why they should not.