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Ca_v1 L‐type Ca²⁺ channels play crucial and diverse roles in the nervous system. The pre‐ and post‐synaptic functions of Ca_v1 channels not only depend on their intrinsic biophysical properties but also their dynamic regulation by a host of cellular influences. These include protein kinases and phosphatases, G‐protein coupled receptors, scaffolding proteins, and Ca²⁺‐binding proteins. The cytoplasmic domains of the main pore forming α₁ subunit of Ca_v1 offer a number of binding sites for these modulators, permitting fast and localized regulation of Ca²⁺ entry. Through effects on Ca_v1 gating, localization, and coupling to effectors, protein modulators are efficiently positioned to adjust Ca_v1 Ca²⁺ signals that control neuronal excitability, synaptic plasticity, and gene expression.