Leukaemia is a devastating disease of the haematopoietic system. The disease develops when mechanisms controlling normal blood production (haematopoiesis) become corrupted. Haematopoiesis critically depends on rare bone marrow (BM)-resident hematopoietic stem cells (HSCs). HSCs possess multiple cell fate choices - they can self-renew, undergo apoptosis, remain quiescent or differentiate into blood lineages. Leukaemia-causing cancer stem cells arise from HSCs or progenitor cells that have gained increased self-renewal and survival capacity and give rise to leukaemic cells. We investigate the regulatory pathways controlling stem cell fate decisions and attempt to understand how these pathways are corrupted to cause leukaemia. We believe that better understanding of cellular and molecular mechanisms underlying stem cell fate decisions will be instrumental in identifying novel therapeutic targets to eradicate cancer stem cells and inhibit leukaemic cell growth.