Neurons generate particular calcium microdomains in response to different stimuli. Calcium microdomains have a central role in a variety of neuronal functions. In particular, calcium microdomains participate in long-lasting synaptic plasticity--a neuronal response presumably correlated with cognitive brain functions that requires expression of new gene products. Stimulation of skeletal muscle generates - with few milliseconds delay - calcium microdomains that have a central role in the ensuing muscle contraction. In addition, recent evidence indicates that sustained stimulation of skeletal muscle cells in culture generates calcium microdomains, which stimulate gene expression but not muscle contraction. The mechanisms whereby calcium microdomains activate signaling cascades that lead to the transcription of genes known to participate in specific cellular responses are the central topic of this review. Thus, we will discuss here the signaling pathways and molecular mechanisms, which via activation of particular calcium-dependent transcription factors regulate the expression of specific genes or set of genes in neurons or skeletal muscle cells.