MicroR159 (miR159) is an ancient family of miRNAs present in all terrestrial plants. It silences a class of genes encoding R2R3 MYB domain transcription factors called GAMYB via highly conserved miR159-binding sites. These GAMYB genes are constitutively transcribed throughout the plant but are totally silenced by miR159. This total silencing is facilitated by conserved RNA 2o structures associated with the miR159-binding site in GAMYB mRNA. Attenuation of this miR159-mediated silencing of GAMYB, either via disruption of the RNA 2o structures or inhibition of miR159 function results in GAMYB protein expression. This results in severe inhibition of plant growth, emphasizing the requirement for GAMYB silencing. However, upon GAMYB protein expression a multitude of genetic pathways involved in pathogen defence are activated, including genes that are involve from microbe to insect resistance. Therefore, miR159 acts as genetic switch from growth to broad-spectrum defense. Functionally verifying this are plants that transiently express GAMYB, resulting in halted growth but which are immune to pathogens. We speculate that the ever-present, but silenced GAMYB transcripts act as a primed sensor of pathogens and insects, where upon attack, the RNA 2o structures sense and alter their structure (riboswitch?) to enable GAMYB expression, leading to a rapid, broad-spectrum defense response. Such a scenario would provide the rationale for the selective advantage of the post-transcriptional silencing of this ever-present GAMYB mRNA.