A series of molecular signals generated as a consequence of a nucleotide-binding domain, leucine rich repeat containing receptor (NLR) binding to one of its physiological ligands. NLRs are cytoplasmic receptors defined by their tripartite domain architecture that contains: a variable C-terminus, a middle nucleotide-binding domain, and a LRR domain that is variable in the repeats composition and number. The NLR signaling pathway begins with binding of a ligand to a NLR receptor and ends with regulation of a downstream cellular process.