This review focuses on the recent advances made in our understanding of the mechanism by which insulin induces the activation of PI 3-kinase(s) whose role is to generate 3-phosphoinositide lipids which are the second messenger of the insulin signalling pathway. The mechanism by which these signalling molecules induce the activation of downstream signalling pathways leading to the activation of protein kinase B (PKB, also known as Akt) and other kinases is also discussed. PKB is likely to be a major mediator of many of the physiological responses of a cell to insulin and likely physiological cellular targets of this enzyme are highlighted.