Calcium (Ca 2+ ) is a ubiquitous second messenger in all eukaryotes. An outstanding question is how this cation serves as a messenger for numerous signals and confers specific cellular responses. Recent studies have established a concept termed ‘Ca 2+ signature’ that specifies Ca 2+ changes triggered by each signal. How do cells recognize these signatures (codes) and translate them into the correct cellular responses? The initial step in this ‘decoding’ process involves sensor proteins that bind Ca 2+ and activate the downstream targets, thereby regulating the specific biochemical processes. Here, I review and discuss a set of Ca 2+ sensors (calcineurin B-like proteins [CBLs]) and their targets (CBL-interacting protein kinases [CIPKs]) as an emerging paradigm for Ca 2+ decoding in plants. The principles governing the action of the CBL–CIPK signaling network could be generally applicable to many other signaling networks in plants and other organisms.