Recurrent aphthous stomatitis (RAS; recurrent aphthous ulcers; canker sores) belongs to the group of chronic, inflammatory, ulcerative diseases of the oral mucosa. Up to now, the etiopathogenesis of this condition remains unclear; it is, however, considered to be multifactorial. The results of currently performed studies indicate that genetically mediated disturbances of the innate and acquired immunity play an important role in the disease development. Factors that modify the immunologic response in RAS include: food allergies, vitamin and microelement deficiencies, hormonal and gastrointestinal disorders (e.g., celiac disease, Crohn's disease, ulcerative colitis), some viral and bacterial infections, mechanical injuries and stress. In this paper, we presented the main etiopathogenetic factors of RAS with a special emphasis on the mechanisms of the immune response modification. Moreover, we discussed the crucial clinical symptoms and types of RAS together with epidemiologic data based on the current medical literature reports and our own observations.