Bacterial ribosomes, composed of proteins and RNA, have been used for nearly 30 years as immunostimulators. Preparations from about 30 different species of bacteria, as well as from fungi or parasites, have been used. Ribosomes have been tested in a number of animal models, and demonstrated to induce both specific immunity and protection. Paradoxically, although only a small part of these studies have dealt with micro-organisms involved in respiratory infections, most of the clinical trials involving ribosomes have used preparations obtained from such bacteria. Ribosomal preparations have been shown to reduce and prevent recurrent infections of the upper respiratory tract in humans. Microbial subcellular fractions induce protective immunity against whole wild-type bacteria, even across serotypic diversities. This observation triggered numerous studies aimed at identifying the immunogenic component of ribosomes. The role of RNA has been ruled out for most species, but it may act as an adjuvant to enhance the immunogenicity of peptide motifs bound to the ribosomes. Finally, although many animal models have used subcutaneous immunisation and intraperitoneal challenge, ribosomal preparations have been shown to be efficient in the more recently explored mucosal routes of vaccination. Oral or intragastric administration of ribosomal preparations actively induces mucosal and protective immune responses against caries or respiratory infections.