Hematopoiesis is a complex process during which hematopoietic stem cells (HSC) proliferate and differentiate to constitute both the myeloid and lymphoid branches of the hematopoietic system. Hematopoiesis occurs in successive organs beginning in the yolk sac and aorto-gonads-mesonephros (AGM) region, then migrate from the AGM region to the fetal liver and subsequently to the bone marrow. Hematopoiesis is regulated by a multitude of signals from the microenvironment that control expansion and proper differentiation of blood progenitors. Modifications in gene expression or protein function, as those occurring by chromosome translocations have an oncogenic potential. Over the last decade an increasing number of recurrent chromosomal translocations has been described that are associated with hematologic malignancies. Cloning of the partner genes in these translocations and molecular abnormalities characterization has provided new insights in the processes involved in both normal and malignant hematopoiesis. We review here some of the translocations involved in the pathogenesis of hematologic malignancies with emphasis on what is known regarding the mechanisms of malignant transformation.