Astrocytes are crucial mediators of brain function. Among other things, they regulate energy metabolism, form the blood-brain barrier, and are essential for synapse formation and maturation of neuronal networks. Astrocytes form a vast network in the brain and signal both with each other and with neurons. Calcium is the primary information carrier in astrocytes. It can be measured with calcium indicators for a functional readout of cellular activity and health. Therapeutic approaches are often designed to influence neurons, but neglect astrocytes, even though they are affected by many drugs, often unintentionally. Analysis of both astrocyte and neuron function is therefore important to implement in drug discovery pipelines. Here we show spontaneous and evoked calcium responses to commonly used reagents in mouse cocultures and human ioAstrocytes, differential effects of aggregated Tau on neurons and astrocytes in mouse cocultures, and spontaneous activity in human neurons grown on ioAstrocytes, to highlight the importance of the transition to human systems for pharmaceutical research.