Chronic mental illnesses are common to find in routine clinical practice and suicide is one of the dreaded outcomes. The concept under defining chronic mental illness has evolved in few decades as now the critical elements for defining the chronic mental illness are psychiatric diagnosis, functional disability, and illness duration. There are various studies on prevalence of suicide and especially in patients with CMI. There is rising trend of research on suicide in patient with psychiatric illness in last decade and found ever over thousand published article in year 2014. This chapter will include literature based on various aspect of suicide including neurobiological factors like neurotransmitters, neural circuits, genetic and epigenetic factors, response on pharmacotherapy and newer generation novel treatment strategies and various psychosocial factors.