The present paper discusses the controversial evidence on cAMP responsive element binding protein (CREB) involvement in different memory processes. Thus, studies have emphasized the role of CREB-mediated transcription in hippocampus-dependent long-term memory (LTM), but not in short-term memory. CREB-mediated transcription has also been shown to be involved in amygdala-dependent LTM, with CREB overexpression in the amygdala proving that it can facilitate LTM formation. Furthermore, a mouse model of Rubinstein-Taybi syndrome supports the role of CREB in LTM formation, rather than in memory acquisition.