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The aim of this review is to explore and summarize the recent advances in pathogenesis, diagnosis, and management of genetically complex autoinflammatory diseases, such as Schnitzler\u2019s syndrome; adult-onset Still\u2019s disease; synovitis, acne, pustulosis, hyperostosis, osteitis syndrome\/chronic recurrent multifocal osteomyelitis\/chronic non-bacterial osteomyelitis; Adamantiades-Beh\u00e7et\u2019s disease; Yao syndrome; and periodic fever with aphthous stomatitis, pharyngitis, and adenitis syndrome. The PubMed database was screened for relevant articles using free text words and specific search strings. The search was limited to English-language articles, reporting the results of studies in humans, published through March 2021. Evidence from literature suggest that these rare multigenic autoinflammatory diseases can present with different clinical features and the diagnosis of these diseases can be challenging due to a combination of nonspecific manifestations that can be seen in a variety of other conditions. Diagnostic delays and disease complications may occur due to low disease awareness and the lack of pathognomonic markers. The pathogeneses of these diseases are complex and in some cases precise pathogenesis is not clearly understood. Conventional treatments are commonly used for the management of these conditions, but biologics have shown promising results. 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