Recent technical and scientific advances in genetics have transformed our understanding of disease in all fields of medicine. In the field of pediatric rheumatology the elucidation of novel monogenic diseases that are characterized by autoinflammation and autoimmunity has provided new fundamental insights into the innate immune system. Autoinflammatory diseases caused by uncontrolled activity of cytokines, such as interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha or type 1 interferon (type 1‑IFN) are amenable to specific therapeutic interventions. Thus, identification of the underlying genetic cause is particularly important and has a great impact on clinical management and decision-making. Clinicians should therefore be familiar with the possibilities and limitations of current molecular genetic methods.