Mental health interventions do not yet offer complete, client-defined functional recovery, and novel directions in treatment research are needed to improve the efficacy of available interventions. One promising direction is the integration of social work and cognitive neuroscience methods, which provides new opportunities for clinical intervention research that will guide development of more effective mental health treatments that holistically attend to the biological, social, and environmental contributors to disability and recovery. This article reviews emerging trends in cognitive neuroscience and provides examples of how these advances can be used by social workers and allied professions to improve mental health treatment. We discuss neuroplasticity, which is the dynamic and malleable nature of the brain. We also review the use of risk and resiliency biomarkers and novel treatment targets based on neuroimaging findings to prevent disability, personalize treatment, and make interventions more targeted and effective. The potential of treatment research to contribute to neuroscience discoveries regarding brain change is considered from the experimental-medicine approach adopted by the National Institute of Mental Health. Finally, we provide resources and recommendations to facilitate the integration of cognitive neuroscience into mental health research in social work.