In 1980, Roger Tsien published a paper, in this journal [Tsien, R. Y. (1980) Biochemistry, 19 (11), 2396], titled "New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures". These new buffers included 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, or BAPTA, which is still widely used today. And so, the world was set alight with new ways in which to visualize Ca²⁺. The ability to watch fluctuations in intracellular Ca²⁺ revolutionized the life sciences, although the fluorescent indicators used today, particularly in neurobiology, no longer rely exclusively on BAPTA but on genetically encoded fluorescent Ca²⁺ indicators. In this Perspective, we reflect on the origins of Ca²⁺ imaging with a special focus on the contributions made by Roger Tsien, from the early concept of selective Ca²⁺ binding described in Biochemistry to optical Ca²⁺ indicators based on chemically synthesized fluorophores to genetically encoded fluorescent Ca²⁺ indicators.