As you work through the chapters in this book it will become very clear that since the beginning of the ‘decade of the brain’ in 1990 we have made considerable progress in understanding how the brain works and the way that it develops across the lifespan. We have also made significant progress in understanding the genetic and environmental factors that contribute to the development of mental health problems. We still, however, struggle to develop new and innovative treatments and therapies and in our understanding of what works for whom in what circumstances – more recently labelled precision or personalized medicine. There are, of course, many factors that contribute to this lack of concrete progress. Psychiatric disorders are complex and heterogeneous across several levels of analysis: phenotypically, with co-morbidity being the rule rather than the exception; aetiologically, with a complex genetic architecture based on different types of genetic variants and gene–environment interplay and diverse brain alterations. Also, as there is no stable, agreed-upon, and biologically valid construct for any of the recognized psychiatric disorders, the current taxonomy provides an unclear basis for informed biological research. Attempts to define biologically homogeneous subtypes (‘biotypes’) or pathophysiological dimensions of psychiatric disorders are under way but have yet to deliver (Feczko et al., 2019). From another angle, enormous scientific challenges are still presented by the complexity of the brain’s architecture and physiology, our far from complete understanding of how these change across development, and the relationships between structure and function and between cognition and behaviour/symptoms. These continue to present enormous scientific challenges.