The dissection of mechanisms that regulate glucose transport by insulin has revealed an intricate network of signaling molecules scattered from the insulin receptor to the intracellular glucose transporter GLUT4. It is also appreciated that some insulin receptor signals jaunt in different directions to regulate events essential for the efficient redistribution of GLUT4 to the plasma membrane. Moreover key assists in the process appear to be arranged by membrane lipids and cytoskeletal proteins. Following current considerations of insulin signals regulating GLUT4, this review will focus on in vitro and in vivo evidence that supports an essential role for phosphoinositides and actin filaments in the control of glucose transport. The discussion will visit recent cell culture, whole animal, and human data highlighting membrane and cytoskeletal aspects of insulin resistance.