To throw light on the superiority of the anti-angiogenesis activity of endostatin (ES) derivatives by reviewing the recent progress in the field of ES molecular structure modification.The data used in this article were mainly from PubMed with relevant English articles published from 1971 to May 2008. The search terms were "endostatin" and "angiothesis".Articles involved in the ES molecular structure modification and the original milestone articles were selected.A number of ES derivatives were designed and studied to improve its clinical relevance. The modified ES with polyethylene glycol (PEG), low molecular weight heparin (LMWH) and IgG Fc domain extended the circulation half-life. Meanwhile the recombinant ESs showed more potent anti-tumor activity than native ES in mouse xenografts. Mutated ES also changed its anti-angiogenesis activity.The anti-angiogenesis treatment remains a promising tumor therapeutic strategy. New ES derivatives would be a good choice to meet the future challenge on clinical application of ES.