Specificity in cell signaling is paramount to plant responses to specific environmental changes. Although calcium is a ubiquitous messenger in plant responses to numerous signals, the mechanism of signal-response specificity remains unclear. Studies in the past four decades in both animal and plant cell models have established the “calcium signature” concept that depicts a distinct calcium change in response to each specific signal. How is a calcium signature encoded by calcium transporters and channels working together and decoded by calcium sensors and their targets represent exciting but challenging questions in the field. Luan lab has been working on both encoding and decoding mechanisms for the past 25 years. Dr. Luan will summarize these research findings to provide a conceptual framework on calcium signaling mechanisms in plants.