Dendritic spines are small actin-rich protrusions from neuronal dendrites that form the postsynaptic part of most excitatory synapses. Changes in the number or strength of synapses are physiological mechanisms behind learning. The growth and maturation of dendritic spines and the activity-induced changes to their morphology are all based on changes to the actin cytoskeleton. In this review, we will discuss the regulation of the actin cytoskeleton in dendritic spine formation and maturation, as well as in synaptic strengthening. Concerning spine formation, we will focus on spine initiation, which has received less attention in the literature. We will also examine the recently revealed regulation of the actin cytoskeleton through post-translational modifications of actin monomers, in addition to the conventional regulation of actin via actin-binding proteins.