Mouse fertilization occurs in the oviduct where spermatozoa bind to the zona pellucida, penetrate the extracellular matrix and fuse with the egg's plasma membrane. Following fertilization, the zona pellucida, is modified to prevent sperm binding and penetration. The molecular basis of these interactions have long intrigued investigators, but remain incompletely understood. The recent use of mouse genetics has prompted review of current knowledge and suggests new models for the critical events for fertilization and early embryo development.