Abstract Voltage‐gated calcium channels (VGCC) are abundant in the central nervous system and serve a broad spectrum of functions, either directly in cellular excitability or indirectly to regulate Ca 2+ homeostasis. Ca 2+ ions act as one of the main connections in excitation–transcription coupling, muscle contraction and excitation–exocytosis coupling, including synaptic transmission. In recent years, many genes encoding VGCCs main α or additional auxiliary subunits have been associated with epilepsy. This review sums up the current state of knowledge on disease mechanisms and provides guidance on disease‐specific therapies where applicable. image