INTRODUCTION Preterm birth is the major cause of perinatal mortality and morbidity in high-income countries. The etiology of preterm birth is multifactorial but there is overwhelming evidence to implicate infection as a major cause. Abnormal genital tract flora in early pregnancy is predictive of preterm birth so it is logical to consider the use of antibiotics for the prevention of preterm birth. AREAS COVERED Infection and antibiotics in the etiology, prediction and prevention of preterm birth. EXPERT OPINION Antibiotics for the prevention of preterm birth have addressed different risk groups, diagnostic methods, degrees of abnormal flora, antibiotic dose regimens, routes of administration, host susceptibilities, host response, gestational age at time of treatment, outcome parameters and definitions of success and outcomes. To address this confusion, a number of systematic reviews/meta-analyses have been conducted but none has simultaneously addressed the optimal choice of agent, patient and timing of intervention. We conclude that inappropriate antibiotics used in inappropriate women at inappropriately late gestations do not reduce preterm birth. Conversely, a focused systematic review/meta-analysis, which targeted the use of clindamycin before 22 weeks gestation, in women with objective evidence of abnormal genital tract flora, demonstrated that clindamycin produced a significant decrease in late miscarriage and preterm birth.