A fundamental mechanism by which cells can give rise to daughters with different fates is via asymmetric division. During asymmetric division, a mother cell generates daughter cells that go on to adopt different fates because of differential segregation of cell fate determinants. Although originally characterized in invertebrates, asymmetric division has recently been shown to regulate cell fate decisions in the mammalian hematopoietic system, playing crucial roles in stem cell renewal, lymphocyte activation, and leukemogenesis. These discoveries have opened new doors to understanding how regulation of division pattern contributes to the normal development and function of the immune system as well as how its dysregulation can lead to cancer.