What is neuroplasticity and what are its origins? These questions have been the subject of intense theoretical and experimental research in the neurosciences for decades. Basically, the term neuroplasticity refers to the ability of neurons to alter some functional property in response to alterations in input. Traditional definitions, however, are often imprecise and restricted to particular ‘model’ neural systems. In the present article we will consider several of the most widely studied models of synaptic-level neuroplasticity including alterations in response properties of two types of invertebrate sensory neurons, long-term potentiation (LTP) in mammalian hippocampus and cortex, and ocular dominance shifts in cat visual cortex. While many other forms of neuroplasticity have been studied, these examples typify the diversity of the subject, as well as illustrate our contention that no unitary model of the phenomena is possible for all conditions. This last point is of particular importance for the mammalian literature, since many hypotheses concerning the mechanism(s) underlying the initiation of neuroplasticity have proposed a single crucial molecular element as the primary causal agent. A closer examination of these various hypotheses, in concert to several examples from the invertebrate literature, leads, however, to the conclusion that synaptic neuroplasticity must arise from a series of inter-related molecular events of a particular form, a cascade, in which individual elements may differ radically from system to system. We next provide an overview of our studies of age-dependent regulation of excitatory and inhibitory ionotropic neurotransmitter receptor populations in cortex in response to agonist and depolarizing stimulation. We provide evidence that such regulation for ionotropic receptors is under the control of ionically driven receptor kinase and phosphatase activity which is also age-dependent in function. These data provide the basis for a cascade model of receptor regulation. Based on this qualitative model, we describe a quantitative computer simulation of certain age-dependent stages in the receptor regulatory cascade which may interact to produce LTP-like effects. While such a model is not exclusive, it nevertheless provides a demonstration that elements in the proposed cascade may comprise the necessary and sufficient conditions for some forms of neuroplasticity. We also propose some of the principles underlying our model as a means of unifying much of the diverse phenomenology reported in the literature. Finally, we make a series of explicit predictions which are testable with current experimental techniques. One prediction which may have important implications for studies of neural recovery is that many forms of critical period neuroplasticity cannot be restored by any real or imagined manipulation of neural molecular or structural elements.