The maturation of the immature oocyte and the fertilization of a mature egg are two absolute prerequisites for mammalian embryo development. There is increasing evidence in mammals that both oocyte maturation and egg activation at fertilization are controlled by changes in intracellular free Ca2+ levels. The role of Ca2+ changes at fertilization is clear in that they are both required and sufficient for egg activation. However, it is not established how the sperm causes Ca2+ changes in eggs at fertilization, nor how different patterns of Ca2+ change affect embryo development. The role of Ca2+ in triggering oocyte maturation is less clear, although preventing intracellular Ca2+ changes can inhibit meiotic maturation at specific stages. Studies on how Ca2+ regulates meiosis and fertilization in mammals may provide new insights into the causes of failed fertilization in human IVF procedures.