Acute and chronic stressors are common triggers of human mental illnesses. Experimental animal models and their cross-species translation to humans are critical for understanding of the pathogenesis of stress-related psychiatric disorders. Mounting evidence suggests that both pharmacotherapy and non-pharmacological approaches can be efficient in treating these disorders. Here, we analyze human, rodent and zebrafish (Danio rerio) data to compare the impact of non-pharmacological and pharmacological therapies of stress-related psychopathologies. Emphasizing the likely synergism and interplay between pharmacological and environmental factors in mitigating daily stress both clinically and in experimental models, we argue that environmental enrichment emerges as a promising complementary therapy for stress-induced disorders. We also call for a broader use of novel model organisms, such as zebrafish, to study such treatments and their potential interplay.