Phosphoinositide 3-kinases (PI3Ks) are crucial for cell proliferation and differentiation during early development, which can make their functions in vivo difficult to study. Heather Bone and Melanie Welham are interested in the roles of class I_A PI3Ks during early development of the haematopoietic system and, on p. 1752, describe a study using embryonic stem (ES) cells and embryoid bodies (EBs). The researchers manipulated PI3K activity both pharmacologically (using a general PI3K inhibitor) and genetically (using ES cells lacking 3-phosphoinositide-dependent protein kinase 1, a kinase downstream of PI3K) and found that PI3K signalling is required for cell proliferation during early development in EBs. They also found that PI3Ks are needed during developmental haematopoiesis, although were surprised to find that PI3K signalling was not necessary early on. Specifically, PI3K signalling is required for the expansion of the blast-colony-forming cells (primitive haematopoietic progenitors) and is involved in haematopoietic cell differentiation – both myeloid and erythroid lineages are affected by reduced PI3K activity. The authors conclude that PI3Ks have several different roles at different times during development of the haematopoietic system.