In many cell types, Ca2+ signals are organized in the form of repetitive spikes. The frequency of these intracellular Ca2+ oscillations increases with the level of stimulation, suggesting the existence of a frequency encoding phenomenon. The question arises as to how the frequency of Ca2+ oscillations can be decoded inside the cell. Ca2+/calmodulin kinase II has long been proposed as an attractive candidate, as it is a key target of Ca2+ signals. By immobilizing the Ca2+/calmodulin kinase II and subjecting it to pulses of Ca2+ of variable amplitude, duration, and frequency, De Koninck and Schulman have shown for the first time that the autonomous activity of Ca2+/calmodulin kinase II is highly sensitive to the temporal pattern of Ca2+ oscillations.