Stromal and epithelial cross-talk plays an important role in the development of female reproductive tract and the pathogenesis of gynaecological disorders. Landmark studies using tissue recombination based-approach showed that the fate of uterine or vaginal epithelium is determined by the respective stromal cells. Additionally, the actions of ovarian hormones on epithelial cells are mediated through the appropriate receptors in stromal cells. In recent years, cell-specific gene knockout mouse models have highlighted that stromal-epithelial communications are essential for implantation, decidualization, and pregnancy. Disruption of these inter-cellular signals is one of the prominent features of many female reproductive tract diseases including infertility, endometriosis, and endometrial cancer. Our recent work has established that age-related changes in stromal cells create growth promoting environment for endometrial epithelial cells leading to their uncontrolled proliferation and cancer. In our most recent work, we have highlighted the significance of stromal cell-derived extracellular matrix in endometrial cell proliferation and invasion.