Recurrent aphthous stomatitis (RAS), commonly known as canker sores, has been reported as recurrent oral ulcers, recurrent aphthous ulcers, or simple or complex aphthosis. RAS is the most common inflammatory ulcerative condition of the oral mucosa in North American patients. One of its variants is the most painful condition of the oral mucosa. Recurrent aphthous stomatitis has been the subject of active investigation along multiple lines of research, including epidemiology, immunology, clinical correlations, and therapy. Clinical evaluation of the patient requires correct diagnosis of RAS and classification of the disease based on morphology (MiAU, MjAU, HU) and severity (simple versus complex). The natural history of individual lesions of RAS is important, because it is the bench mark against which treatment benefits are measured. The lesions of RAS are not caused by a single factor but occur in an environment that is permissive for development of lesions. These factors include trauma, smoking, stress, hormonal state, family history, food hypersensitivity and infectious or immunologic factors. The clinician should consider these elements of a multifactorial process leading to the development of lesions of RAS. To properly diagnose and treat a patient with lesions of RAS, the clinician must identify or exclude associated systemic disorders or "correctable causes." Behçet's disease and complex aphthosis variants, such as ulcus vulvae acutum, mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome, fever, aphthosis, pharyngitis, and adenitis (FAPA) syndrome, and cyclic neutropenia, should be considered. The aphthous-like oral ulcerations of patients with human immunodeficiency virus (HIV) disease represent a challenging differential diagnosis. The association of lesions of RAS with hematinic deficiencies and gastrointestinal diseases provides an opportunity to identify a "correctable cause," which, with appropriate treatment, can result in a remission or substantial lessening of disease activity.