Cellular immediate-early genes are rapidly and transiently activated when cells are stimulated with many different growth factors. This review examines the function of a short immediate-early gene regulatory sequence, the Serum Response Element (SRE), that is sufficient for this transient transcriptional activation. The structures of SREs and SRE-containing promoters are presented, followed by a summary of SRE regulatory properties. The roles of other SRE-like regulatory sequences in mammalian and yeast cells are then considered. The properties of SRE binding proteins are reviewed, followed by a discussion of the effects of mutations on both SRE function and protein binding. Finally, possible models for SRE function are discussed.