Despite the wide variety of tissue-engineered vascular grafts that are currently being developed, autologous vessels, such as the saphenous vein, are still the gold standard grafts for surgical treatment of vascular disease. Recently developed technologies have shown promising results in preclinical studies, but they still do not overcome the issues that native vessels present, and only a few have made the transition into clinical use. The endothelial lining is a key aspect for the success or failure of the grafts, especially on smaller diameter grafts (<5 mm). However, during the design and evaluation of the grafts, the mechanisms for the formation of this layer are not commonly examined. Therefore, a significant amount of established research might not be relevant to the clinical context, due to important differences that exist between the vascular regeneration mechanisms found in animal models and humans. This article reviews current knowledge about endothelialization mechanisms that have been so far identified: in vitro seeding, transanastomotic growth, transmural infiltration, and fallout endothelialization. Emphasis is placed on the models used for study of theses mechanisms and their effects on the development of tissue-engineering vascular conduits.