Preterm birth (PTB) is globally the leading cause of death and disability in children under five years of age. Intra‐amniotic infection is well recognised as a major cause of PTB. Importantly, it is the most common cause of extreme PTB (birth prior to 28 weeks gestation), which is frequently associated with a wide range of serious neonatal morbidities. Recent developments in next generation sequencing technologies, combined with many years of culture‐based microbiological data have allowed us to gain a deeper understanding of the pathogenesis of infection‐mediated PTB. In particular, studies have revealed numerous potential routes to intra‐amniotic infection beyond the classically described ascending vaginal route. Currently, antibiotic therapy is standard treatment for suspected or confirmed intra‐amniotic infection, although its use in this context has had mixed success due to problems ranging from inappropriate antibiotic selection in relation to the target organism/s, to poor transplacental drug passage. In this review, we will draw together evidence from animal models and human studies to characterise pathways to intra‐amniotic infection. We will then thoroughly outline current therapeutic protocols for cases of intra‐amniotic infection and suggest potential new avenues for treatment.