This paper deals with the effects of bicarbonate induced signaling pathways on plasma membrane lipid organization and downstream protein signaling, and their role in sperm-egg interactions. It also provides an overview of results that indicate that bicarbonate responses are not related to cell death or apoptosis. The information presented shows that only those sperm cells that have functionally completed maturation in the epididymis are sensitive to bicarbonate whereas immature sperm fail to respond to this physiological challenge. Therefore, it is important to selectively analyze the responsive sperm subpopulations when studying sperm capacitation. Moreover, bicarbonate induced signaling responses differ within the diverse sperm structures (e.g. the tail versus the head). Consequently, dissecting sperm structures and signaling areas from each other deserves more attention in sperm capacitation research. The information discussed was obtained from a variety of mammalian species but the basic bicarbonate-mediated sperm responses are similar in most Eutherian species despite some species to species variations (most notably in kinetics rather than the sequence of events). The objective of the paper is to provide a comparative experimental overview of bicarbonate mediated sperm capacitation in the hope that this information will lead to a better understanding of the complex biochemical nature of the involvement of bicarbonate in mammalian sperm capacitation.