Plant resistance proteins directly or indirectly perceive the presence of pathogen virulence factors and trigger an effective form of plant immunity that often includes programmed host cell death. Because the activation of resistance proteins has the potential to be detrimental to the plant, this process is tightly regulated on multiple levels. Several resistance genes have been shown to be alternatively spliced. Depending on the resistance gene, alternative transcripts are thought to limit the expression of R proteins or encode truncated R proteins with a positive role in defense activation. In addition, R gene alternative splicing is dynamic during the defense response. Possible mechanisms of R gene alternative splicing regulation and how alternative R gene transcripts fit into the current view of resistance protein-mediated defense responses are discussed.