Toxoplasma gondii is an obligate intracellular parasite that can infect any nucleated cell. The parasite invades host cells, replicates inside a parasitophorous vacuole and egresses to invade more host cells. This lytic cycle is associated with the tissue damage that accompanies the acute infection and is linked to the pathology of toxoplasmosis. Fluctuations of cytoplasmic Ca2+ are linked to the activation of the cellular processes involved in each step of the lytic cycle. However, the mechanism by which cytoplasmic Ca2+ is stimulated preceding egress is unknown. Using genetic Ca2+ indicators expressed in the cytosol of the parasites and also in the host cell, we show that cytoplasmic Ca2+ increases in the intracellular parasites prior to both artificially stimulated and natural egress. We demonstrated that extracellular Ca2+ entry enhances the events surrounding egress and that specific Ca2+ peaks observed prior to egress could correspond to signaling pathways regulating this step.