Circulating monocytes are believed to be committed precursors for phagocytes, such as macrophages and dendritic cells. Recently, we have reported a primitive human cell population called monocyte-derived multipotential cells (MOMC), which has a fibroblast-like morphology and a unique phenotype positive for CD14, CD45, CD34, and type I collagen. This novel cell type exhibits mixed morphologic and phenotypic features of monocytes, endothelial cells, and mesenchymal cells. MOMC are derived from circulating CD14⁺ monocytes, and their differentiation requires binding to fibronectin and exposure to one or more soluble factors derived from peripheral blood CD14^- cells. MOMC contain progenitors with capacity to differentiate into a variety of non-phagocytes, including bone, cartilage, fat, skeletal and cardiac muscle, neuron, and endothelium. Recent studies by others have also described several distinct human cell populations that are originated from circulating monocytes and have capacity to differentiate into non-phagocytes. These observations together indicate that circulating monocytes are more multipotential than previously thought. In addition, cell transplantation therapies using circulating monocytes are a potential approach for tissue regeneration.