Currently becoming widely recognized, personalized psychiatry focuses on patients’ unique physiological and genetic profiles to best tailor their therapy. However, the role of individual differences, as well as genetic and environmental factors, in human psychiatric disorders remain poorly understood. Animal experimental models are a valuable tool to improve our understanding of disease pathophysiology and its molecular mechanisms. Due to high reproduction capability, fully sequenced genome, easy gene editing and high physiological homology with humans, zebrafish (Danio rerio) are emerging as a novel powerful model in biomedicine. Mounting evidence support zebrafish as a useful model organism in CNS research. Robustly expressed in these fish, individual, strain and sex differences shape their CNS responses to genetic, environmental and pharmacological manipulations. Here, we discuss zebrafish as a promising translational tool to further advance patient-centered personalized psychiatry.