Voltage-gated calcium channels mediate intracellular Ca2+ influx and are absolutely critical for the physiological function of excitable cells in brain, skeletal, cardiac and smooth muscle, endocrine glands, and other tissues. These membrane proteins translate membrane depolarization signals into rapid, local increases in cytoplasmic calcium concentration that can trigger key events such as excitability, exocytosis, contraction, migration, and gene transcription. This chapter reviews basic structural features and functional properties of Ca2+ channels that confer their remarkable selectivity, modulation properties, and responses to therapeutic drugs. The diversity of Ca2+ channels is considered in the context of their varied functional roles, their molecular subunits, and the dysfunction of these subunits in disease states. The latter part of this chapter reviews key physiological processes using particular channel types to exemplify their function and discusses recent information obtained from genetic models and diseases that arise from genetic and acquired abnormalities in Ca2+ channel function.