Mucosae constitute the major entry for most microbial pathogens but also innocuous antigens derived from ingested food, airborne matter or commensal bacteria. A large and highly specialized innate and adaptative mucosal immune system protects the mucosal surfaces and the body interior from potential injuries from the environment. The mucosal immune system has developed a variety of immune mechanisms to discriminate between non-pathogenic and pathogenic invaders. It is able to maintain tolerance against the plethora of environmental antigens and to induce potent protective immunity to avoid mucosal colonisation and organism invasion by dangerous microbial pathogens. Mucosal immunisation with appropriate antigens and immunostimulatory molecules may induce potent protective immunity against harmful pathogens. Alternatively, mucosally-induced tolerance against auto-antigens or allergens may be generated by mucosal administration of these antigens alone or with immunomodulators potentiating regulatory responses. Here, we review the properties of the mucosal immune system and briefly discuss the advances in the development of mucosal vaccines for protection against infections and for the treatment of inflammatory disorders such as autoimmune diseases or type I allergies.