The G protein-coupled receptors (GPCRs) are the most numerous and the most diverse type of receptors (1–5% of the complete invertebrate and vertebrate genomes). They transduce messages as different as odorants, nucleotides, nucleosides, peptides, lipids, and proteins. There are at least eight families of GPCRs that show no sequence similarities and that use different domains to bind ligands and activate a similar set of G proteins. Homo- and heterodimerization of GPCRs seem to be the rule, and in some cases an absolute requirement, for activation. There are about 100 orphan GPCRs in the human genome which will be used to find new message molecules. Mutations of GPCRs are responsible for a wide range of genetic diseases. The importance of GPCRs in physiological processes is illustrated by the fact that they are the target of the majority of therapeutical drugs and drugs of abuse.