Humans and laboratory animals display cognitive deficits as they age. However, there are currently no effective therapies available to treat these deficits, as the underlying mechanisms are poorly understood. Studies using pharmacological compounds have found a link between cognitive performance and the intrinsic cellular excitability of CA1 hippocampal neurons. Therefore, it is of great interest to identify molecular regulators that may be influencing both cognition and neuronal excitability, which could be changed with age. One possible regulator is the transcription factor cAMP response element binding-protein (CREB). In young adult animals, manipulation of CREB activity has resulted in modulation of both cognitive performance on behavioral tasks, and neuronal excitability. While evidence is sparse, studies also point to a dysfunction in CREB signaling with aging. We propose that CREB may be a viable therapeutic target for the treatment of age-related cognitive deficits, along with potential experiments to test this hypothesis.