Recent studies brought the evidences that some cell surface molecules associated with immune system (cluster of differentiation (CD) molecules) may be involved in the fertilization process. The experimental observations regarding the function of CD9, CD49f/CD29, CD46 and CD11b/CD18 have led to the construction of general hypothesis of fertilization comprising the interaction of these CD molecules in binding and fusion of sperm and egg. The models for the role of CD9 and CD49f/CD29 in the fertilization are based on the interaction of tetraspanin CD9 and integrin alpha6beta1 (CD49f/CD29) via fertilin in sperm-egg binding and fusion. The model for the role of integrin CD11b/CD18 and CD46 in fertilization is based on the interaction of these two molecules through complement C3 fragments which may serve as bridging ligands between sperm CD46 and oocyte CD11b/CD18 and facilitate apposition of the sperm inner acrosomal membrane with oolemma.