One of the most fundamental events in eukaryotic biology is the fusion of two cells to produce a single cell. Fertilization, the fusion of two haploid gametes to create a diploid zygote, is the basis of sexual reproduction, without which none of us would be here. However, cell fusion is not limited to fertilization, but plays important roles during vertebrate development and disease. For example, becoming competence to fuse is part of the differentiation pathway of cells destined to become muscle fibers. For both yeast and vertebrate cells, differentiating cells exit the cell cycle and acquire new functions. The coordination of differentiation and cell division is of vital importance; one hallmark of cancer is the loss of differentiated functions with the renewed capacity for proliferation. Similarly, when yeast cells mate, they must carefully coordinate the transition from the mitotic pathway into the mating pathway. Indeed, many of the proteins required for mating have other essential functions in mitosis, and cells must prevent their premature co-option into the mating pathway. Because several genes required for yeast conjugation have close homologs in all eukaryotic organisms, it is likely that the rules governing the transition from mitosis to mating will be generally applicable. We are exploring these questions by analyzing two of the major steps in yeast mating; cell fusion and nuclear envelope fusion.