Plants have evolved sophisticated surveillance systems to recognize conserved microbial patterns or secreted pathogen effector proteins. Research in Arabidopsis has significantly advanced our understanding of plant immune perception and signaling. Intracellular immune receptors possessing central nucleotide binding and C-terminal leucine rich repeat domains (NLR) recognize pathogen effector proteins delivered inside host cells during infection. Characterized NLRs can either directly or indirectly recognize corresponding pathogen effector proteins. Despite the conserved domain architecture of NLRs, no unified model exists for induction of downstream signaling. NLRs have diverse subcellular localizations, including targeting to the endoplasmic reticulum, plasma membrane, nucleus, and cytosol. This review will focus on our current understanding of NLR biology, from signal perception to downstream immune outputs.