An oocyte's journey is highly distinct from the vast majority of cells in the body. As one of the largest and rarest cells, oocytes express unique genes required for the genesis of healthy and competent eggs. The function of only a handful of oocyte-specific genes is beginning to be unraveled. Transgenic mouse models have proven to be extremely valuable in studying the effects of gene deletions on oocytes and surrounding somatic cells. Growth differentiation factor 9 (Gdf9), bone morphogenetic protein 15 (Bmp15), zona pellucida genes (Zp1, Zp2 and Zp3), factor in the germline alpha (Figla), and the c-mos protooncogene (c-mos) are some of the genes preferentially expressed in oocytes which play important roles during folliculogenesis. In order to identify other novel genes preferentially expressed in oocytes, we have utilized subtractive hybridization and in silico subtraction. The combination of these identification approaches, coupled with the use of knockout mice, will lead to many future functional studies of genes uniquely devoted to oogenesis and folliculogenesis.