Recurrent oral ulceration that clinically resembles recurrent aphthous stomatitis but presents atypically, including commencement after adolescence, with fever, with a strong family history, or failing to resolve with age, has been termed aphthous-like ulceration (ALU). It may be seen in some immunodeficiency states, chronic viral infections, rheumatologic disorders, skin diseases, and the periodic syndromes. The periodic syndromes, considered to be the prototypic autoinflammatory diseases, present with recurrent short attacks of myalgia, arthralgia, rashes, abdominal pain, lymphadenopathy, and fever. Several of the syndromes can result in amyloidosis. Genetic studies have enhanced the clinical characterization of these conditions and elucidation of their molecular etiopathogenesis. This paper describes 2 patients with periodic syndromes presenting with ALU and reviews the present understanding of the syndromes.