Multiple eukaryotic cell processes are modulated by calcium ions (Ca2+). As such, Ca2+ is emerging as a crucial regulator of innate immunity in multicellular organisms. In particular, recent studies have identified roles of Ca2+ signalling at the host-bacteria interface. Following microbial exposure, Ca2+ signals mobilised from the extracellular milieu or intracellular stores are transduced into cell physiological responses. However, during infection with host-adapted pathogens, Ca2+ signals are often atypical, due to the activities of virulence factors, with varied consequences for both the pathogen and the host cell. In this review, we describe the Ca2+-dependent host factors regulating antibacterial immunity, in addition to bacterial effectors that promote, inhibit, or co-opt Ca2+-calmodulin signalling to promote infection.