In the modern globalized world with rapid industrialization and urbanization the city has once again become the focus of modern social, economic and political life. Urban spaces and places have been the focus of research by many disciplines, including epidemiology, sociology, anthropology, and urban studies. In this chapter, the authors outline the importance and the role of culture in urban mental health employing various historical, sociological, and epidemiological contexts. The authors point out that modern multicultural approaches in viewing the metropolis can be conceptualized as a global hub of migration. This therefore becomes a place where individuals encounter the other and various boundaries between spaces and residence, and between wellness and illness, intersect. Acculturation to the urban places may take some time and the authors propose that the psychological process of acculturation is a useful beginning in terms of unpicking and understanding the phenomenology of identity formation and cross-cultural contact. The chapter traces the historical development of the city in parallel to the literature on psychosis and the city in developed and developing contexts, before critically examining the role of culture in informing our explanatory and interpretive frameworks of psychosis epidemiology.