This chapter starts defining spirituality as a transcendent realm of reality, which is considered sacred, and religion as the institutional or communal aspect of that spirituality. Then, it explores whether and how issues relating to religion and spirituality (R/S) are relevant to the mental health of individuals. A large body of evidence is presented and discussed showing that R/S remain and probably will continue to be relevant in the contemporary world, and that R/S have marked and usually positive effects on mental health. Ethical concerns regarding approaching R/S in clinical care are addressed, arguing that this approach must be patient-centred. An evidence-based, and ethically sound, bio-psycho-socio-spiritual approach is proposed. In summary, in respect to the evidence available and the R/S beliefs, behaviours and values of most of the world’s population, it is not only appropriate but a scientific and ethical duty to integrate R/S into mental health research, training, prevention, and clinical practice.