Recent studies of molecular mobility in the plasma membrane have revealed that diffusion is restricted by cytoskeletal networks or fences. Transmembrane protein “pickets” that reversibly associate with the membrane-associated skeleton and with the pericellular coat impede the movement of unattached bystander molecules. While membrane picket-fences were originally described as barriers to free diffusion in more passive cell types such as fibroblasts, they have particularly important functions in the more dynamic immune cells. In phagocytes, such fences curtail spontaneous activation and their disassembly facilitates stimulation by target particles, fostering receptor clustering and the exclusion of phosphatases from the phagocytic cup. In this review, we describe the nature of the cellular cytoskeleton and of the exoskeleton created by the pericellular coat, their association with transmembrane pickets, and the modulation of molecular mobility during phagocytosis.