Until the past few years, it has been thought that lymphoid and myeloid lineage segregation represents the first step of lineage restriction during hematopoiesis from hematopoietic stem cell. Recent investigation of the cell populations within multipotent progenitors in the bone marrow has led to new understanding of how hematopoietic stem cells diversify into different hematopoietic cell types. This review focuses on the recent advances in understanding the developmental events that occur during hematopoietic stem cell specification into the T and B lymphocyte lineages in adult mice.