The innate immune system relies on the recognition of pathogens by pattern recognition receptors as a first line of defense and to initiate the adaptive immune response. Substantial progress has been made in defining the role of Nod (nucleotide-binding oligimerization domain)-like receptors and AIM2 (absent in melanoma 2) as pattern recognition receptors that activate inflammasomes in macrophages. Inflammasomes are protein platforms essential for the activation of inflammatory caspases and subsequent maturation of their pro-inflammatory cytokine substrates and induction of pyroptosis. This paper summarizes recent developments regarding the function of Nod-like receptors in immunity and disease.