Successful implantation and pregnancy requires sufficient decidualization and a subtle embryo–maternal dialogue. Numerous factors are active in a dense network; their interactions and their possible impact on therapeutic approaches will be described. Decidualization is triggered primarily by sexual steroid hormones, estrogens, and progestins, but also by growth factors, cytokines, other signalling pathways, and immunological processes. Important signals are the IGF (insulin-like growth factor) system, the TGF (transforming growth factor)-β family, and prostaglandins. The degree of decidualization can be described by biomarkers like prolactin, IGFBP (insulin-like growth factor-binding protein)-1, LEFTY2 (NODAL-signaling pathway inhibitor left–right determination factor) or by histological dating. Apposition, attachment, and implantation of the human embryo involve for example selectins, integrins, and HB-EGF (heparin-binding EGF-like growth factor). To analyze endometrial receptivity, gene expression tests are currently in clinical trials. However, no proven therapeutic concepts to improve receptivity and implantation have been established up to now. Intravenous infusion of fatty emulsions in cases with overexpression of uterine NK (natural killer) cells or endometrial scratching are widely used. Treatment with corticoids or acetylsalicylic acid failed to give positive effects.