Immunity towards bacteria might be achieved as a result of natural processes following infection, or as a consequence of medical intervention including vaccination, administration of immunoglobulins or therapy with immunostimulants derived from bacteria. Bacterial immunostimulants (ISs) containing bacterial lysate (OM-85 BV, LW 50020) or components of bacterial cells (ribosomal extracts) were shown to induce a non-specific response (i.e. intensification of phagocytosis) but also to orchestrate both cellular (B, T cell stimulation) and humoral responses (antibodies and proinflammatory cytokines production). Therefore, the duality of their immunomodulatory activity mimics or, to a certain extent, repeats the immune response evoked by the intrusion of a pathogen into the human body, which is initially non-specific, but subsequently becomes specific. However, their clinical efficacy in the prevention of respiratory tract infection (RTI) is still debated. This article reviews their mechanism of action, as well as the available clinical data, discussing the pros and cons of their use in the prevention of RITs in children and adults.