Sexually transmitted infections (STIs) have been part of human life since ancient times, and their symptoms affect quality of life, and sequelae are common. Socioeconomic and behavioural trends affect the prevalence of STIs, but the discovery of antimicrobials gave hope for treatment, control of the spread of infection and lower rates of sequelae. This has to some extent been achieved, but increasing antimicrobial resistance and increasing transmission in high-risk sexual networks threaten this progress. For Neisseria gonorrhoeae, the only remaining first-line treatment (with ceftriaxone) is at risk of becoming ineffective, and for Mycoplasma genitalium, for which fewer alternative antimicrobial classes are available, incurable infections have already been reported. For Chlamydia trachomatis, in vitro resistance to first-line tetracyclines and macrolides has never been confirmed despite decades of treatment of this highly prevalent STI. Similarly, Treponema pallidum, the cause of syphilis, has remained susceptible to first-line penicillin.