Chronic pain remains a very difficult condition to manage for healthcare workers and patients. Different options are being considered and a biopsychosocial approach seems to have the most benefit, since chronic pain influences biological, psychological and social factors. A conservative approach with medication is the most common type of treatment in chronic pain patients; however, a lot of side effects are often induced. Therefore, a premium is set on novel nonpharmacological therapy options for chronic pain, such as psychological interventions. Previous research has demonstrated that resilience is a very important aspect in coping with chronic pain. A more recent type of cognitive-behavioural therapy is Acceptance and Commitment Therapy, in which psychological flexibility is intended to be the end result. In this manuscript, current evidence is used to explain why and how a comprehensive and multimodal treatment for patients with chronic pain can be applied in clinical practice. This multimodal treatment consists of a combination of pain neuroscience education and cognitive-behavioural therapy, more specifically Acceptance and Commitment Therapy. The aim is to provide a clinical guideline on how to contribute to greater flexibility and resilience in patients with chronic pain.