Heterotrimeric G-proteins are important signalling proteins which function in all cells of the mammalian organism. Inactivating mutations in a variety of G-protein alpha-subunit genes in mice resulted in mostly unexpected phenotypes and have provided interesting new insight into their biological roles. Whereas the inactivation of some G alpha genes led to mild phenotypes suggesting the presence of redundant or compensatory mechanisms, other G-proteins appear to play highly specific biological or developmental roles. The purpose of this review is to summarize the current knowledge about G-protein functions based on gene-inactivation studies.