Patients with psychiatric illness present a unique challenge to clinicians: in contrast to the traditional medical model, in which patients are conceptualised as being stricken by a disease, patients with certain psychiatric illnesses may seem complicit in the illness. Questions of free will, choice and the role of the physician can cause clinicians to feel helpless, disinterested or even resentful. These tensions are a lasting legacy of centuries of mind–body dualism. Over the past several decades, modern tools have finally allowed us to break down this false dichotomy. Integrating a modern neuroscience perspective into practice allows clinicians to conceptualise individuals with psychiatric illness in a way that promotes empathy and enhances patient care. Specifically, a strong grasp of neuroscience prevents clinicians from falling into the trap in which behavioural aspects of a patient's presentation are perceived as being separate from the disease process. We demonstrate the value of incorporating neuroscience into a biopsychosocial formulation through the example of a ‘difficult patient’.