The structure of dendritic spines is highly plastic and responds to synaptic activity, including activity patterns that induce long-term potentiation (LTP) and depression (LTD). Induction of LTP causes enlargement of spine heads, while LTD causes spine head shrinkage. In addition, spine structure is well associated with synaptic weight and the extent of synaptic plasticity, such that structural changes of the spine may represent forms of memory storage. While the correlation between structural and functional plasticity appears to be simple, the underlying mechanisms of spine plasticity are intricate. Spine plasticity requires multiple molecular interactions, and is affected by the surrounding environment and by cellular metabolic state. Here, I synthesize the latest progress in this field by defining six determinants of spine plasticity, and discuss the role of each factor in memory storage.