Introduction: Hereditary periodic fevers (HPFs) are inherited errors of the innate immunity which, although individually uncommon, collectively have set up a novel emerging and developing chapter of pediatrics. Areas covered: A careful analysis and identification of diseases globally known as HPFs is essential to prompt an effective treatment and improve survival and quality of life of these children. This review provides a detailed summary of the main monogenic autoinflammatory disorders appearing with recurrent fevers in childhood with the final aim to help pediatricians in a correct recognition and discrimination of hereditary causes of fever. Expert opinion: Challenges associated with the management of monogenic autoinflammatory disorders in childhood have been increasingly tantalized by the different treatment options available and by the recently accessible genetic investigation techniques, which have led to identify a growing number of rare causes of periodic fevers. In addition, as new mechanisms underlying the regulation of innate immunity are discovered and more pathogenetic therapeutic approaches are adopted, the next decade promises a progress in the knowledge of HPFs and a potential genomically-based therapeutic approach. Actually, the inhibition of interleukin (IL)-1 represents the most incisive treatment for patients with HPFs who do not respond to standard therapies or for whom the administration of canonical drugs is unsuitable and characterized by secondary effects.