During brain maturation, neurons form specific connections with each other to establish functional neuronal circuits. The processes underlying the development of connectivity, such as the selection of synaptic partners and the fine-tuning of neuronal networks, act with single-synapse precision. Calcium is an intracellular secondary messenger that operates with remarkable spatio-temporal specificity and regulates functional and structural adaptations at the level of individual synapses. Although the structure, molecular composition and function of an emerging synapse changes dramatically during its development, the single-synapse specificity of calcium signaling is maintained at every step of synapse formation: when the first contacts between axons and dendrites form, during the onset of synaptic function and later, when spine synapses emerge. Here, we describe the mechanisms that help developing neurons to confine calcium signaling to individual synapses, and discuss how these local calcium dynamics facilitate the development of accurate neuronal connections at each step of synapse maturation.