A distinction between short-term memories lasting minutes to hours and long-term memories lasting for many days is that the formation of long-term memories requires new gene expression. In this review, the focus is on the current understanding of the relation of transcription to memory consolidation based on the data collected from behavioral studies performed primarily on genetically altered animals. Studies in Drosophila and Aplysia indicate that the transcription factor cAMP/Ca2+ response element binding protein (CREB) is critical in mediating the conversion from short- to long-term memory. More recent genetic studies in mice also demonstrated CREB and inducible transcription factor Zif268 involvement in information storage processes. Transcription seems to play essential role in memory formation but the mechanisms for activation of transcription and downstream processes during memory consolidation remain unclear.