Peripheral blood is a large accessible source of adult stem cells for both basic research and clinical applications. Peripheral blood mononuclear cells (PBMCs) have been reported to contain a multitude of distinct multipotent progenitor cell populations and possess the potential to differentiate into blood cells, endothelial cells, hepatocytes, cardiomyogenic cells, smooth muscle cells, osteoblasts, osteoclasts, epithelial cells, neural cells, or myofibroblasts under appropriate conditions. Furthermore, transplantation of these PBMC-derived cells can regenerate tissues and restore function after injury. This mini-review summarizes the multi-differentiation potential of PBMCs reported in the past years, discusses the possible mechanisms for this multi-differentiation potential, and describes recent techniques for efficient PBMC isolation and purification.