The introduction of novel technologies, including high resolution time lapse imaging in behaving animals, molecular modification of the genome and optogenetic control of neuronal excitability have revolutionized the ability to detect subcellular changes in the brain, associated with learning and memory. The sequence of molecular cascades leading to formation, longevity and erasure of memories are being addressed in growing number of studies. Still, major issues concerning the relationship between the morphology and physiology of dendritic spines and memory mechanisms and the functional, neuronal network relevance of such parameters remain unsettled. The present review will summarize recent studies related to the immediate and long lasting changes in density, morphology and function of dendritic spines and their parent neurons following exposure to plasticity-producing stimulation in vivo and in vitro. Standing issues such as the relations between volume/shape and longevity, with respect to different classes of memories in different brain regions will be addressed. These studies indicate that the rules governing the structure/function relations of dendritic spines and memory in the brain are still not conclusive.