Inflammation is the body’s response to injury, pathogen exposure, and irritants. Pattern recognition receptors allow our body to recognize a diverse array of patterns generated during exposure to these insults. In 2002, thenucleotide-binding domainleucine-richrepeat-containing (NLR, also known as NOD-like receptor) gene family of pattern recognition receptors was discovered (1-3). While several members were already recognized at that point, reports of the entire NLR family provided a global view. In the past 15 years of research, the physiological relevance of these genes has been revealed to include a diverse variety of functions. Gene mutations in some of the family members have been linked to autoinflammatory diseases in humans (Fig. 1). This association of mutations in NLR genes to autoinflammatory diseases indicates critical functions in the regulation of immunity and inflammation. © 2017 American Society for Microbiology, Washington, DC.