Adaptation to living with cardiovascular disease may differ from patient to patient and is influenced not only by disease severity and limitations incurred by the disease but also by socioeconomic factors (e.g. health literacy), the patients’ psychological make-up and susceptibility to distress. Co-morbid depression and/or anxiety is prevalent in 20% of patients with cardiovascular disease, which may be either transient or chronic. Distress, such as depression, reduces adherence, serves as a barrier to behaviour change and the adoption of a healthy lifestyle, and increases the risk that patients drop out of cardiac rehabilitation, impacting on patients’ quality of life, risk of hospitalisation and mortality. Hence it is paramount to identify this subset of high-risk patients in clinical practice. This review provides a general overview of the prevalence of selected psychosocial risk factors, their impact on patient-reported and clinical outcomes, and biological and behavioural mechanisms that may explain the association between psychosocial factors and health outcomes. The review also provides recommendations on which self-report screening measures to use to identify patients at high risk due to their psychosocial profile, and the effectiveness of available trials that target these risk factors. Despite challenges and barriers associated with screening of patients combined with appropriate treatment, it is paramount that we treat not only the heart but also the mind in order to improve the quality of care and patient and clinical outcomes.