Recent experimental results on spike-timing-dependent plasticity (STDP) and heterosynaptic interaction in various systems have revealed new temporal and spatial properties of activity-dependent synaptic plasticity. These results challenge the conventional understanding of Hebb's rule and raise intriguing questions regarding the fundamental processes of cellular signaling. In this article, I review these new findings that lead to formulation of a new set of cellular rules. Emphasis is on evaluating potential molecular and cellular mechanisms that may underlie the spike-timing window of STDP and different patterns of heterosynaptic modifications. I also highlight several unresolved issues, and suggest future lines of research.