James Glazier Indiana University Biocomplexity Institute The construction, maintenance and disruption of tissues emerge from the interactions of cells with each other, the extracellular microenvironment that the cells create and their external boundary conditions. Our ability to make biomedically meaningful predictions at the organ or organism level is limited because of the difficulty of predicting the emergent properties of large ensembles of cells. A middle-out approach to model building starting from cell behaviors and combining subcellular molecular reaction kinetics models, the physical and mechanical behaviors of cells and the longer range effects of the extracellular environment, allows us to address such emergence. I will discuss CompuCell3D as a multi-scale, multi-cell modeling platform to study such emergent phenomena and to connect them to their physiological outcomes. I will illustrate two projects using CompuCell3D, the development and of blood vessels and its effect on the growth of a generic model solid tumor and Choroidal Neovascularization (CNV) in Age-Related Macular Degeneration (the most common cause of blindness among the elderly). The AMD simulations suggest novel drug targets for improved therapeutic outcomes. Time permitting, I will also briefly discuss our proof-of-concept simulations of somatic evolution in solid tumors.