During hematopoiesis, hematopoietic stem cells (HSCs) gradually lose their multi-potency and ultimately commit to a single lineage at certain period in the maturation process. Before entering the lineage commitment stage, progenitors have to go through multiple specification steps. During this progression, both external and internal cues may have effects on the cell fates of progenitors. However, it is not clear how extrinsic signals such as cytokines or growth factors from the microenvironment and intrinsic cell differentiation programs are coordinated and determined for lineage specification and commitment during hematopoiesis. Nevertheless, it has been assumed that upon lineage commitment, progenitors follow a hierarchical and linear differentiation program. Recently, the issues of developmental plasticity or latent differentiation potential in lineage-committed progenitors have been documented, although lineage commitment has been thought to be an irreversible event. Therefore, we may need to revisit the issue of how “lineage commitment” is determined in the hematopoietic system at the molecular level. In this review, we would like to propose a revised model for lineage commitment and give an overview of recent advances in understanding how lineage decision is made.