Ovulation is essential for reproductive success; many cases of infertility in women may be related to disruption of this critical and complex ovarian process. Recent gene profiling studies using rat, mouse, and human ovaries and cumulus oocyte complexes isolated prior to, during, and following luteinizing hormone (LH or human chorionic gonadotropin) -induced ovulation have unmasked a surprising diversity and staggering number of genes for which expression is altered in these tissues. Thus, impairment of this process could involve many factors not yet considered. Although some genes associated with inflammatory-like responses have been identified previously and shown to be obligatory for ovulation, others represent entirely new categories of genes. These include genes associated with innate immune responses and immune cell functions, neuronal cell activity, and novel signaling cascades. The innate immune and neuronal genes are expressed in cumulus cells not adhering immune cells. Thus, cumulus cells acquire immune cell-related functions. The neuronal-related genes may influence cumulus cell migration during formation of the hyaluronan-rich matrix. The factors stabilizing the matrix are essential for expansion of the cumulus oocyte complex and release of a fertilizable oocyte contained therein. Novel signaling molecules include members of the WNT/FRIZZLED family, the BMP family, and transcription factors. Some of these novel genes may become useful predictors of ovulation success and/or embryo health and viability.