Mental health and wellbeing are the critical basis by which humans can flourish, fulfil their potential, and remain resilient in the face of stress and adversity. However, mental disorders are one of the leading causes of disability worldwide. In Arctic and Subarctic regions, these challenges are particularly pressing because of the rapid social and cultural changes and their impacts on the wellbeing of Indigenous populations. Improving our capacity for diagnosis and treatment in multiple populations is crucial and requires new knowledge of the biological roots and sex-based differences of mental health problems, new early-detection methods, and new environmental and biological mechanisms that can be targeted for intervention. Moreover, sociocultural and environmental factors influence mental health and need to be considered as determinants of health. Within this holistic understanding of mental wellness, access to culturally and environmentally appropriate housing is of major concern for northern communities. This chapter gathers a selection of Sentinel North research results from a broad range of disciplines that aim to improve our understanding of mental health issues and wellbeing in northern communities. Results range from the discovery of new biomarkers for the early diagnosis and treatment of mental disorders, to culturally sensitive interventions that address key determinants of health and the advancement of ecosystem-based approaches to mental health and resilience.