Cell-based therapy has emerged as a promising option for treating advanced ischemic cardiovascular disease by inducing vascular regeneration. However, clinical trials with adult cells turned out disappointing in general. As a newer approach, direct reprogramming has emerged to efficiently generate endothelial cells (ECs), which can promote neovascularization and vascular regeneration. This review provides recent updates on the direct endothelial reprogramming. In general, directly reprogrammed ECs can be generated by two approaches: one by transitioning through a plastic intermediate state and the other in a one-step transition without any intermediate states toward pluripotency. Moreover, the methods to deliver reprogramming factors and chemicals for the fate conversion are highlighted. Next, the therapeutic effects of the directly reprogrammed ECs on animal models are reviewed in detail. Other applications using directly reprogrammed ECs, such as tissue engineering and disease modeling, are also discussed. Lastly, the remaining questions and foremost challenges are addressed.