Environmental stimulation throughout development adjusts the neurobehavioral systems involved in learning, memory and defensive responses. Environment-mediated phenotypic plasticity can be considered from two different, yet complementary, viewpoints. On one hand, the possibility that environmental interventions protect against the effects of genetic and/or acquired vulnerabilities, offers unprecedented avenues towards the elaboration and refinement of therapeutic strategies. On the other hand, an accurate understanding of the adaptive mechanisms regulating the interaction between an experimental subject and its environment may substantially benefit the quality of experimental data. Here we review experimental evidence showing that enriched environment can be beneficial in several psychiatric and neurodegenerative disorders implicating the monoamine systems where it can (i) compensate for impairments in animal models of schizophrenia, Huntington's, and Parkinson's diseases; (ii) increase resistance to the addictive properties of psychostimulant drugs; (iii) level-out the consequences of prenatal stress in animal models of depression. Additionally we discuss why some of the effects of environmental enrichment question the validity of current animal models of mental disorders.