Endothelial damage and dysfunction are implicated in cardiovascular pathological changes and the development of vascular diseases. In view of the fact that the spontaneous endothelial cell (EC) regeneration is a slow and insufficient process, it is of great significance to explore alternative cell sources capable of generating functional ECs to repair damaged endothelium. Indeed, recent achievements of cell reprogramming to convert somatic cells to other cell types provide new powerful approaches to study endothelial regeneration. Based on progress in the research field, the present review aims to summarize the strategies and mechanisms of generating endothelial cells through reprogramming from somatic cells, and to examine what this means for the potential application of cell therapy in the clinic.