Although our perspective does not minimize the relevance of IGF-targeted therapies, we propose that the analysis of IGFBP2 proteolysis will provide major contributions to properly modify or implement current strategies, such as the value of specific proteolytic inhibitors or even the use of optimized IGF-binding partners to prevent an excessive bioavaibility of IGFs to tumor cells. The gene discussed is IGFBP2; the disease is neoplasm.