The cervical mucus plug is a large, complex structure within the cervical canal that is shed shortly before or during labor. We propose that the cervical mucus plug fulfills critical ‘gate-keeper’ functions based on its physical and immunologic properties, which help prevent ascending infection and preterm labor. The viscoelastic properties of the cervical mucus plug are determined by mucins (large glycoproteins), which can inhibit viral replication and exclude larger molecules and bacteria by preventing their diffusion through the plug. Furthermore, the innate and adaptive immunological properties of the cervical mucus plug are well suited for arresting bacterial infection by stimulating a robust inflammatory response. A possible association between an impaired gate-keeper function of the cervical mucus plug and preterm birth is discussed.