Studies using different diagnostic methods and outcome parameters have used different antibiotics and dose/administration regimes to women of differing risk of preterm birth with, not surprisingly, different results. Studies which have shown benefit have been criticised for having either poor methodology, low sample size or having only showed benefit after a non-prespecified subgroup analysis. Studies which have failed to show any benefit have been criticised for unacceptable methods of diagnosing abnormal genital tract flora or having excluded a large percentage of patients eligible for the study, for having permitted a long period to elapse from diagnosis of abnormal genital tract flora to administration of treatment and for having employed treatment too late in pregnancy. A Cochrane Systematic Review of these studies failed to provide a definitive answer because this was published one month before two randomised double-blind placebo-controlled trials were published, in which clindamycin used either systemically or intravaginally in low risk, unselected women resulted in a 60% reduction in the incidence of preterm birth. This would have influenced the inconclusive results of the Cochrane review, with respect to general population studies. Very early spontaneous preterm labour and preterm birth is more likely to be of infectious aetiology than preterm birth just before term. The earlier in pregnancy at which abnormal genital tract flora is detected, the greater is the risk of an adverse outcome. Women with abnormal flora in early pregnancy, who subsequently revert to normal, continue to have a high risk of adverse outcome of pregnancy, at a degree similar to women with abnormal genital tract flora in early pregnancy who were treated with placebo. This suggests that whatever damage abnormal flora induces, this is at an early gestation, even if the flora subsequently reverts to normal. It follows therefore that if antibiotics are to be of help in preventing spontaneous preterm labour and preterm birth of infectious aetiology, these must be administered early in pregnancy. Antibiotics used prophylactically for the prevention of preterm birth are more likely to be successful if: they are used in women with abnormal genital tract flora (rather than other risk factors for preterm birth, e.g. low BMI, twins, generic previous preterm birth); they are used early in pregnancy prior to infection (tissue penetration/inflammation and tissue damage); they are used in women with the greatest degree of abnormal genital tract flora; and if they are used in women with a predisposition to mount a damaging inflammatory response to infection.