As pointed out by Auerbach in 1991 "Perhaps the most consistent limitation to progress in angiogenesis research has been the availability of simple, reliable, reproducible, quantitative assays of the angiogenesis response." In vitro angiogenesis assays, based on endothelial cell cultures or tissue explant, focus on isolated endothelial cell functions (e.g., endothelial cell proliferation, migration, or invasion) and do not examine the coordination of cell functions required for a successful angiogenic response (Jain et al., 1997; Auerbach et al., 2000). Although in vitro angiogenesis assays have been useful for identi cation of potential molecular targets to block endothelial cell responses and preliminary screening of novel pharmacological agents, they frequently cannot be correlated with in vivo angiogenesis measurements. This is most likely the result of the c- plex and multiple cellular mechanism evoked during new blood vessel formation in vivo. In vitro assays cannot be considered conclusive and the activity of a compound must be con rmed in other assays of increasing complexity, including in vivo assays of angiogenesis, angiogenic-dependent tumor growth, and metastasis.