Syphilis, cholera and TB have re-emerged and now affect the health of countless humans globally. In this article, we review current information concerning the biology and epidemiology of these bacterial diseases with the goal of developing a better understanding of factors that have led to their resurgence and that threaten to compromise their control. The impact of microbial and environmental change notwithstanding, the main factors common to the re-emergence of syphilis, cholera and TB are human demographics and behavior. This information is critical to developing targeted strategies aimed at preventing and controlling these potentially deadly infectious diseases.