Abstract: “Mice are not little people” – a refrain becoming louder as the strengths and weaknesses of animal models of human disease and drug responses become more apparent. At the same time, three emerging approaches are headed toward integration: powerful systems biology analysis of cell-cell and intracellular signaling networks in patient-derived samples; 3D tissue engineered models of human organ systems, often made from stem cells; and micro-fluidic and meso-fluidic devices that enable living systems to be sustained, perturbed and analyzed for weeks in culture. Endometriosis, adenomyosis, and other gynecological disorders are paradigms of chronic inflammatory diseases that can only partially be modeled in animal systems. In this talk, approaches to classify patients on the basis of analysis of cell-cell communication networks will be described as a motivation for building patient avatars that capture salient features of the disease processes. Then, approaches to use synthetic extracellular matrices to build tissue-engineered models of the endometrium and endometriosis lesions, including microvascular networks and immune cell recruitment, will be highlighted, along with the potential to integrate these approaches for developing new drugs to treat endometriosis and adenomyosis.