The endometrium maintains complex controls on proliferation and apoptosis as part of repetitive menstrual cycles that prepare the endometrium for the window of implantation and pregnancy. The reliance on inflammatory mechanisms for both implantation and menstruation creates the opportunity in the setting of endometriosis for establishment of chronic inflammation that is disruptive to endometrial receptivity, causing both infertility and abnormal bleeding. Clinically, there can be little doubt that the endometrium of women with endometriosis is less receptive to embryo implantation, and strong evidence exists to suggest that endometrial changes are associated with decreased cycle fecundity as a result of this disease. Here we provide unifying concepts regarding those changes and how they are coordinated to promote progesterone resistance and estrogen dominance through aberrant cell signaling pathways and reduced expression of key homeostatic proteins in eutopic endometrium of women with endometriosis.