The concept that blood cells arising from hematopoietic stem cells (HSC) can be subdivided into two major lineages, a myelo-erythroid and a lymphoid lineage, has long persisted. Indeed, it has become almost axiomatic that the first branch point from the HSC produces two progenitors, one for myelo-erythroid cells and the other for lymphoid cells. However, recent studies have provided a battery of findings that cannot be explained by this classical model. We will outline how this classical model arose before describing how we came to propose an alternative ‘myeloid-based model’, in which myeloid potential is retained in erythroid, T, and B cell branches even after these lineages have segregated from each other.