Sexually transmitted infections (STIs) have plagued humans for millennia and can result in chronic disease, pregnancy complications, infertility, and even death. Recent technological advances have led to a better understanding of the causative agents for these infections as well as aspects of their pathogenesis that might represent novel therapeutic targets. The articles in this Review Series provide excellent updates on the recent advances in understanding of the pathogenesis of some very important and persistent STIs and discuss the importance of considering each pathogen in the broader context of the environment of the individual who it infects.