The endometrium is a dynamic tissue that facilitates mammalian internal reproduction and thus, the ability to deliver live born progeny that are more easily protected from predators. This tissue is unique in its ability to undergo cyclic regeneration and destruction in the absence of pregnancy. Ovarian steroids guide endometrial proliferation and maturation promoting its receptivity and selectivity with regards to blastocyst implantation. It is decidualization, terminal stromal maturation, that prevents the trophoblast from breeching containment of the uterus and allows for endometrial sloughing should pregnancy not occur. Endometrial pathology is highly variable and therefore a wide array of diagnostic measures are required for its interrogation. There remains no single test that can distinguish between all potential issues and it is critical that appropriate and evidence-based endometrial assessment is carried out. Emerging data on developmental markers, inflammatory mediators, and bacterial profiling offer hope that conditions including endometriosis, cancer, infertility, and implantation failure will be more easily and less invasively diagnosed. This will allow for a more timely and targeted approach to intervention. Accordingly, assessing novel measures requires an evidence-based approach prior to their mass utilization.