At fertilization of the mammalian egg, the spermatozoon initially binds to and then fuses with the egg plasma membrane. This critical event activates specific biochemical pathways within the egg. Activation of the egg induces resumption of meiosis and the start of rapid embryonic mitotic divisions on the one hand, and cortical granule exocytosis leading to modification of the zona pellucida and a block to polyspermy on the other. It has been shown in different systems that changes in intracellular ion concentrations can serve as second messengers of signal transduction mechanisms. The use of specific fluorescence probes, combined with the image analysis technique, facilitates the measurement of their dynamics in real time in the living cell and, thereby, assessment of their role in activation of the mammalian egg. This review focuses on the dynamics of intracellular Ca2+ and pH and their role in transducing the sperm signal to downstream cell cycle regulators.