Many immune cells can detect the direction and intensity of an extracellular chemical gradient, and migrate toward the source of stimulus. This process, called chemotaxis, is essential for immune system function and homeostasis, and its deregulation is associated with serious diseases. Chemotaxis is initiated by chemoattractant binding to heterotrimeric G protein-coupled receptors, which translate the gradients into accurate directional migration. A necessary step in this process is cell polarization, the acquisition of functional and spatial asymmetry. The use of new imaging technologies enables analysis of spatial and temporal changes in the activity of proteins and membrane domains involved in polarization and chemotaxis. We discuss the sometimes contradictory evidence available and the emerging molecular model for immune cell polarity and chemotaxis.