Cells are capable of responding to extracellular stimuli because of their ability to detect external information and to transduce this signal to intracellular effectors that may result in the generation of second messengers and/or cause alteration in the cell’s metabolism. The cell surface receptors are responsible for detecting the external information and a group of proteins, termed GTP-binding proteins, are responsible for receptor-effector coupling. In eukaryotic cells, there are two major families of GTP-binding proteins (G proteins) that participate in the various signal transduction pathways (Bourne et al., 1990 , 1991 ). The first family consists of the heterotrimeric (αβγ-subunit structure) GTP-binding proteins, which link cell surface receptors to effectors inside the cell (Birnbaumer et al., 1990 ; Neer, 1995 ; Rens-Domiano and Hamm, 1995 ). The second family includes GTP-binding proteins that consist of a single polypeptide chain and are commonly referred to as the small-mol-wt G proteins (Grand and Owen, 1991 ; Valencia et al., 1991 ; Takai et al., 1992 ; Bokoch and Der, 1993 ). This chapter will deal with the characterization and possible function(s) of small-mol-wt G proteins in mammalian cells.