Phosphatidylinositol 3-kinases (PI3Ks) generate lipids that are implicated in receptor-stimulated signalling and in the regulation of cell growth/differentiation and cellular function. Several pathways have been recently identified and this article summarizes current knowledge about them. Depending on cell type the PI3K pathway has been involved in positive or negative regulation of differentiation. Products of PI3Ks and other signalling intermediates are shared between the G protein-coupled receptors and receptor tyrosine kinases, suggesting that control of differentiation and growth is equally dependent on these two distinct classes of receptors. Thus, the role of PI3Ks in the regulation of differentiation is clearly a very complex process implicating integration between different receptor systems and cell type-specific responses.