Decreasing the burden of stress-related mental problems and diseases is seen by many as one of the greatest health care challenges of the 21st century. Figures show that (each year) 60.4 million people (14% of the EU population) suffer from anxiety disorders, while major depression affects 29.8 million people (6.9%). Critically, stress-related symptoms tend to become chronic diseases, highlighting the need for early interventions to prevent their development. Efforts toward prevention are, however, hampered by a lack of understanding of the factors that determine resilience to stressors. The STRESNET project has made a major contribution to filling this gap by first detailing the effects of stress on brain function, with a focus on global shifts in brain function at the level of large-scale brain networks. Second, it identified the specific networks that are associated with resilience to real-life stressors, using mobile applications for self-report mood questionnaires and wearable biosensors. Third, the project has developed a novel biofeedback intervention based on real-time functional MRI to specifically target these brain networks, and showed that healthy volunteers can be trained to self-regulate brain activity at the level of balance between these brain networks. Together, these efforts provide a scientific foundation for future efforts toward mental health prevention in individuals at risk for development of stress-related diseases.