The United States is 25 years into a large-scale drug overdose epidemic, yet its consequences for gender differences remain largely unexplored. This study finds that drug overdose mortality increased seven- and fivefold for men and women, respectively; accounts for 0.8-year (men) and 0.4-year (women) deficits in life expectancy at birth in 2017; and has made an increasing contribution (from 1 percent to 17 percent) to women's life expectancy advantage at the prime adult ages between 1990 and 2017. I document a distinctive cyclicality to sex differences in drug overdose. During the epidemic's early stages - the heyday of prescription opioids - gender differences narrowed, but once the epidemic transitioned to illicit drugs in 2010, gender differences widened again. This pattern holds across racial/ethnic groups, and in fact may be even stronger among Hispanics and non-Hispanic Blacks than among non-Hispanic Whites. That we observe this gender dynamic across racial/ethnic groups is surprising since very different trends in drug overdose mortality have been observed for Whites versus other groups. The contemporary epidemic is a case of dynamic change in gender differences, and the differential mortality risks experienced by men and women reflect gendered social norms, attitudes towards risk, and patterns of diffusion.