As immunologists, we evaluate patients with a large spectrum of disorders, which include impaired immunity, autoimmunity, and autoinflammatory features. Recent discoveries in inflammatory pathways have elucidated disease pathogenesis and also treatment targets to best focus on the most involved cytokine pathways. Autoinflammatory diseases center around the inability to quell a nonantigenic inflammatory response due to missing suppressive components of the immune system. Management is mostly directed to minimize the sequelae of uncontrolled, chronic inflammation. In this article, an array of classic periodic fever syndromes will be discussed along with disorders involving dysregulated IL-1, TNF, NF-kb, and Type 1 interferon pathways.