Pluripotency refers to the ability of a cell to give rise to cells that originate from all three germ layers. Among the available human pluripotent cells, human embryonic stem cells (hESCs) are considered to have the greatest probability for practical clinical application because of their simple propagation and stability in culture. Since their first derivation, issues concerning hESC maintenance and self-renewal have been widely addressed. The first part of this review presents the accumulated knowledge concerning the self-renewal of hESCs and discusses recent genetic profile data, which seem to shed light on hESC self-renewal and pluripotency mechanism. The second part deals with the regenerative potential of hESCs. Available lineage-specific differentiations of hESCs are presented, with detailed data on the ability of hESCs to differentiate into trophoblast cells, an observation that might broaden the definition of their developmental potential. Specific focus is given to vascular cell differentiation, including endothelial and smooth muscle cells. Transplantation limitations as well as current steps taken toward resolution conclude the review.