Recent progress on the understanding of leukocyte signal transduction pathways indicates that many of these pathways are modulated by low-molecular-weight GTP-binding proteins (LMWGs). LMWGs are members of a growing family of GTP-binding proteins known as the pas superfamily and act as molecular switches for regulating a wide range of signal-transduction pathways in virtually all cells. In leukocytes, LMWGs have been shown to participate in essential cellular functions such as growth control, differentiation, cytoskeletal organization, cytokine and chemo attractant-induced signaling events, reduced nicotinamide adenine dinucleotide phosphate oxidase activity, phospholipid metabolism, and intracellular vesicle transport and secretion, and many more of these functions will certainly be identified as we gain a further understanding of regulatory pathways modulating leukocyte signal transduction. This review will summarize our current understanding of this rapidly advancing area of research.