Blood forming system is one of the most complicated system in our body. Everyday, more than 10 distinct types of blood cells are generated from one specific cell type, hematopoietic stem cells, through multiple steps of cell division and maturation. This process is called differentiation. Interestingly, hematopoietic stem cell also provide itself when a stem cell divide into two daughter cells without differentiation. This ability is called self-renewal. In the blood forming system, hematopoietic stem cells take balance between self-renewal and differentiation to maintain proper blood formation throughout our life. We reviewed current understanding of the structure of blood forming system and molecular mechanisms regulating self-renewal and differentiation of hematopoietic stem cell.