Calcium is an essential macronutrient and a second messenger for signal transduction in plants. Apart from acting as a second messenger, calcium is also required for cytoskeleton, cell division, pollen tube growth and as a co-factor. Cytoplasmic calcium ion ([Ca 2+ ] cyt) is maintained at a low level, however, is rapidly elevated using storages in organelles on perception of a stimulus. Ca 2+-binding proteins that sense the kinetics and magnitude of elevated [Ca 2+ ] cyt convert the chemical signals to biological signals and define specificity of responses. These proteins are broadly classified into sensor relays and sensor responders. Sensor relay proteins require another interacting protein to transmit the signal; whereas, the sensor responders combine within one protein the relay, amplification and response functions. A significant achievement has been made in the last three decades that identified and characterized various proteins instrumental in decoding Ca 2+-signals in plant cells. The latest addition in Ca 2+-signaling is Calcineurin B-like proteins (CBLs) and their interacting kinases (CIPKs). It is believed that flexibility of interactions between different CBL and CIPK proteins and their sub-cellular localizations are crucial in sensing and responding to specific signals. In this review, we have laid emphasis on the recent and emerging advancements in understanding of the CBL-CIPK module.