Synaptic plasticity, the activity dependent change in synaptic strength, forms the molecular foundation of learning and memory. Synaptic plasticity includes structural changes, with spines changing their size to accomodate insertion and removal of postynaptic receptors, which are correlated with functional changes. Of particular relevance for memory storage are the long lasting forms of synaptic plasticity which are protein synthesis dependent. Due to the importance of spine structural plasticity and protein synthesis, this review focuses on the signaling pathways that connect synaptic stimulation with regulation of protein synthesis and remodeling of the actin cytoskeleton. We also review computational models that implement novel aspects of molecular signaling in synaptic plasticity, such as the role of neuromodulators and spatial microdomains, as well as highlight the need for computational models that connect activation of memory kinases with spine actin dynamics.