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The massive reemergence of diphtheria in the Newly Independent States of the former Soviet Union marked the first large-scale diphtheria epidemic in industrialized countries in 3 decades. Factors contributing to the epidemic included a large population of susceptible adults; decreased childhood immunization, which compromised what had been a well-established childhood vaccination program; suboptimal socioeconomic conditions; and high population movement. The role of a change in the predominant circulating strains of Corynebacterium diphtheriae in this epidemic remains uncertain. Massive, well-coordinated international assistance and unprecedented efforts to vaccinate adults were needed to control the epidemic.