Nitric oxide (NO) and hydrogen peroxide (H 2O 2) are 2 key elements in heat shock (HS) signaling pathway. Our experiments indicate the existence of a cross talk among H 2O 2, NO, Ca 2+ channels, and the activation of calmodulin (CaM) to stimulate the DNA-binding activity of HS transcription factors as well as the accumulation of HS proteins so as to confer thermotolerance. CaM can bind to target proteins to alter their function, acting as part of a calcium signal transduction pathway. However, only a few of its target proteins had been reported by now. Herein we are discussing them and conclude that in order to obtain a more profound understanding of CaM signaling, further research will be needed in the future.