Angiogenesis is a fundamental prerequisite for tissue growth and thus an attractive target for cancer therapeutics. However, current efforts to halt tumor growth using antiangiogenic agents have been met with limited success. A reason for this may be that studies aimed at understanding tissue and organ formation have to this point utilized two-dimensional cell culture techniques, which fail to faithfully mimic the pathological architecture of disease in an in vivo context. In this issue of Tissue Engineering, the work of Fischbach-Teschl's group manipulate such variables as oxygen concentration, culture three-dimensionality, and cell-extracellular matrix interactions to more closely approximate the biophysical and biochemical microenvironment of tumor angiogenesis. In this article, we discuss how novel tissue engineering platforms provide a framework for the study of tumorigenesis under pathophysiologically relevant in vitro culture conditions.