The voltage-gated calcium channel α₂δ and β subunits are traditionally considered to be auxiliary subunits that enhance channel trafficking, increase the expression of functional calcium channels at the plasma membrane and influence the channels' biophysical properties. Accumulating evidence indicates that these subunits may also have roles in the nervous system that are not directly linked to calcium channel function. For example, β subunits may act as transcriptional regulators, and certain α₂δ subunits may function in synaptogenesis. The aim of this Review is to examine both the classic and novel roles for these auxiliary subunits in voltage-gated calcium channel function and beyond.