This chapter sets a backdrop to how practitioners need to consider how one of the fastest growing research paradigms in the field of mental health in recent years impacts professional practice. The chapter sets out to examine what role neuroscience could play in the formulation process for people with mental health disorders experiencing psychological distress. Research has examined the role that genes, proteins, neurotransmitters, structural, functional, and interconnectivity abnormalities influence mental health and illness. It indicates the utility of incorporating a neuroscience perspective into case formulation within mental health practice and shows that the maximal utility of such findings is through its synthesis with other aspects of the assessment process. The chapter is a reminder that what we deal with and try to understand as practitioners is often heavily influenced by a ‘back story’ that is becoming more accessible with technological and neuroscientific advances. It highlights that it is not a person's genetic makeup, or the events that they have experienced that precipitate mental health problems but rather the complex interplay between genetics, environmental factors, and the meaning that a person attaches to a particular set of experiences that generates distress.