Abstract: Early postnatal stimulation, e.g., neonatal handling (NH) in its most frequent form, and environmental enrichment (EE, the exposure of juvenile animals, usually during several weeks, to environments involving rich and variable sensory stimulation) produce profound and long-lasting behavioral and neurobiological effects. Both treatments reduce anxiety and stress sensitivity, and improve neurodevelopment and learning/memory in unconditioned and conditioned tasks in laboratory rodents. In addition, both manipulations lead to long lasting ‘‘protective’’ effects against age-related hippocampal neurodegeneration, cognitive deficits and associated stress-related neuroendocrine processes (e.g., Meaney et al., 1988; Fernández-Teruel et al., 1997, 2002). The present commentary is focused on summarizing relevant evidence on the enduring positive effects of early enriched sensory (NH- or EE-like) stimulation on neurobehavioral development and neuroplasticity (including the promotion of neural regeneration or the prevention of neurodegeneration) in rodents, and to discuss the possible clinical relevance and translatability of similar treatment approaches to humans.