Plant nucleotide-binding, leucine-rich repeat receptors (NLRs) perceive pathogen avirulence effectors and activate defense responses. Nucleotide-binding, leucine-rich repeat receptors are classified into coiled-coil (CC)containing and Toll/interleukin-1 receptor (TIR)-containing NLRs. Recent advances suggest that NLR CC domains often function in signaling activation, especially for induction of cell death. In this review, we outline our current understanding of NLR CC domains, including their diversity/classification and structure, their roles in cell death induction, disease resistance, and interaction with other proteins. Furthermore, we provide possible directions for future work.