The respiratory system is permanently exposed to the influence of numerous harmful environmental factors: various microbial pathogens, allergens and air pollution, with non-volatile toxic chemicals of tobacco smoke. Therefore, there have been developed several mechanisms protecting from these factors. These mechanisms can be classified as innate, non-specific, or acquired, much more specific, which are associated with regular immune response. In this review authors shortly describe the innate, non-specific mechanisms, which compose the first line of antimicrobial defense in our respiratory system. The mechanisms of innate immunity include passive protection, provided by the mucus-mediated mechanical barrier. Moreover, by means of active defense, several potent immunoregulatory factors and various substances displaying antibacterial, antifungal and antiviral activity are also engaged.