The status of a woman’s cervicovaginal microbiome may correlate with the risk of obstetric complications such as isthmic cervical insufficiency (ICI) and preterm delivery (PD). This review examined the relationship between the microbiome and ICI. The dominance of Lactobacillus crispatus and, possibly, L. gasseri in the microbiome was associated with full-term pregnancy, whereas the predominance of other Lactobacillus species and anaerobic bacteria led to the preterm rupture of membranes and PD. Notably, high levels of the antimicrobial peptide β-defensin 2, even without L. crispatus dominance, are also associated with full-term pregnancy. The analysis of the cervicovaginal and amniotic fluids of women who subsequently gave birth prematurely revealed an increase in the levels of proinflammatory cytokines, such as interleukin (IL)-2, IL-8, and IL-10. Changes in the microbiome composition and an increase in the maternal immune response lead to premature remodeling and softening of the cervix, i.e. ICI. Thus, early detection of changes in the cervicovaginal microbiome and cervicovaginal and amniotic fluids may be a prognostic marker for ICI and PD.