Ca²⁺ is one of the most ancient and ubiquitous second messengers. Highly polarized pancreatic acinar cells serve as an important cellular model for studies of Ca²⁺ signalling and homeostasis. Downstream effects of Ca²⁺ signalling have been and continue to be an important research avenue. The primary functions regulated by Ca²⁺ in pancreatic acinar cells – exocytotic secretion and fluid secretion – have been defined and extensively characterized in the second part of the last century. The role of cytosolic Ca²⁺ in cellular pathology and the related question of the interplay between Ca²⁺ signalling and bioenergetics are important current research lines in our and other laboratories. Recent findings in these interwoven research areas are discussed in the current review.