Mental disorders are increasingly recognized to be chronic and disabling, belonging to a group of serious medical illnesses including heart disease, cancer and diabetes (Insel and Scolnick, 2006; Mathers and Loncar, 2006). The Global Burden of Disease report has revealed that neuropsychiatric conditions account for a quarter of all disability-adjusted life years (Prince et al., 2007). Furthermore, the burden of mental disorders is likely to be underestimated because of inadequate appreciation of the link between mental illness and other health conditions. Several health conditions increase the risk for mental disorder and co-morbidity complicates help-seeking, diagnosis and treatment and can affect prognosis. An often underestimated risk factor for mental health has to do with exposure to maternal or nutritional perinatal conditions, as well as exposure to early stress. For the most common major illnesses, we now have medical and psychosocial interventions of proven efficacy in randomized, controlled trials. Many patients with mood disorders will respond to treatment and some will recover completely. However, the available treatments appear still insufficient, thus urging a more effective bridge between basic research discoveries and the development of novel therapeutic strategies for the cure and prevention of mental illnesses. One the limiting factors for developing appropriate therapeutic strategies could derive from the notion that researchers have so far approached mental illnesses as fundamentally different from all other medical diseases (Insel and Scolnick, 2006). These considerations have prompted us to deal with these issues by soliciting a number of contributions from researchers involved in basic research in mental health. The aim of this Special Issue of Neuroscience and Biobehavioral Reviews is to give an overview of how different approaches can be used in translational neuroscience in order to facilitate the identification of vulnerability factors, novel diagnostic markers as well as pharmacological targets to be exploited by the pharmaceutical industry for the development of innovative preventive approaches and treatment strategies. Within this issue studies performed in humans (Gerra et al., 2007; Andersen and Teicher, 2008) provide a clear evidence that exposure to adverse events during the course of development predispose an individual to substance abuse. Understanding the role that development plays in the expression of these risk factors is often overlooked, but definitively needs more attention to fully understand the impact of early life events on the complex neurobiological derangement, including HPA axis and dopamine system dysfunctions, playing a crucial role in addictive and affective disorders - and possibly metabolic -susceptibility. Despite the important information provided by human studies, these have a limited capacity to explain basic mechanisms of disease. In this issue we included a number of papers demonstrating how, in recent years, there has been a growing emphasis on developing complex models that incorporate a number of variables which can be manipulated by the experimenter thus providing new opportunities for translation from basic to clinical research. We will provide examples of studies performed with the common aim of understanding the role of environmental/nutritional factors in shaping brain development and functioning. While studies performed using rodents (Alleva and Francia, 2008; Andersen and Teicher, 2008; Cirulli et al., 2008) offer a great opportunity to ask questions that can be answered in a short-time scale and allow for the analysis of neurobiological substrates, (Coccurello et al., 2008; Laviola et al., 2008; Marco et al., 2008; Nag et al., 2008; Scattoni et al., 2008) those using non-human primates offer a great opportunity to ask questions that can be answered in a short-time scale and allow for the analysis of neurobiological substrates, those using non-human primates provide the closest match to humans in terms of genetic, behavioral, biological and social similarity (Cirulli et al., 2008). In addition, non-human primates’ relatively long lifespan, extended infancy, and socio-affective behavior parallel many aspects of human development. The challenge that basic science needs to meet is to make use of a comparative approach to benefit the most from what each model, notwithstanding its constraints, can tell us about the mechanisms underlying an increased risk for mental health.