The normal functioning of tissues depends on the availability of an adequate supply of oxygen and nutrients. This is maintained by the vasculature, comprising of arteries, arterioles, capillaries and postcapillary venules that finally drain into the veins. The implication of endothelial cells in the process of angiogenesis has resulted in extensive studies using this cell type. Microvascular endothelial cells are primarily involved in mounting a neovascular response. Current methods use colorimetric assays such as those based on the conversion of tetrazolium salts to colored formazan salts by functional mitochondria, but fluorescence techniques, such as using Alamar blue, are more sensitive. Matrigel is a potent inducer of endothelial cell differentiation, and is mainly composed of collagen IV and laminin, and containing heparan sulfate, proteoglycans, and nidogen or entactin in small quantities. The integration of endothelial cells in multicellular spheroids was found to inhibit apoptosis and induce cellular differentiation, and appropriate tension in the matrix led to the sprouting of capillaries from these spheroids. The current models for studying angiogenesis can be classified into three categories, such as the excision of vascularised tissues, microcirculatory preparations, and implant assays. In chronic transparent window models, windows containing grids with cancer cells or factors to be studied are placed in the skin or the mesentery. Exterior tissue preparations explain chorio-allantoic membrane assay. The most commonly used assay in this category is the chick chorioallantoic membrane (CAM) assay, in which the shell of fertilised eggs are opened to expose the chorioallantoic membrane, and discs with modulating factors are placed on the membrane.