Recurrent implantation failure (RIF) is a source of distress and frustration to both patients and their clinicians. In the absence of clinically useful tests, the therapeutic approach has been largely empirical, with limited efficacy. In recent years, new insights into the role of the endometrium in implantation have emerged, and a number of dysfunctions that may underlie implantation failure have been characterized. These point to the presence, in some patients, of an underlying endometrial pathology. In this article, the case is made that constitutive (rather than maturation) defects underlying RIF can be identified. Evidence is presented of a specific transcriptomic signature that is highly predictive of RIF.