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The innate immune system, and in particular dysregulation of the interleukin-1 (IL-1) pathway, plays a central role in the pathogenesis of many pediatric rheumatic disorders that are broadly classified as autoinflammatory disorders. Many of these disorders have a genetic etiology and despite affecting a few key immunologic pathways, distinct patterns of tissue specificity have emerged. Chronic recurrent multifocal osteomyelitis (CRMO, also called chronic nonbacterial osteomyelitis) is the most common autoinflammatory disorder that targets the bone. Recent advances in the understanding of CRMO have led to the identification of disease-associated genes (LPIN2, Pstpip2, IL1RN), cytokine dysregulation including the importance of IL-1 in bone inflammation, and the intriguing finding that diet can prevent inflammation of the bone in a murine model of the disease.