This paper suggests that our intuitive use and understanding of the concepts defence and safety can be opened up to more systematic study and theory. This may provide a powerful framework for biopsychosocial approaches in clinical psychology. Defence and safety can be seen as two fundamental, evolutionary adaptive, information-organizing systems. The operation of these two systems has major effects on biological patterns, social behaviour, relationships and the maturation of self-constructs. It is suggested that many forms of psychopathology represent the activation of evolved, defensive strategies. This paper explores the organization and operation of these two systems and attempts to integrate data from neuropsychological work with ideas from evolutionary theory and social psychology on the effects of threat sensitivity and defensiveness, and safety. It is suggested that interpersonal threats are the most common sources of human defensive behaviour and these are often about separation-rejection or power and subordination. In the latter part of the paper discussion will be on the way people try to create safe environments by putting others down, or by submitting to more powerful others.