Population neuroscience endeavours to identify environmental and genetic factors that shape the function and structure of the human brain; it uses tools and knowledge of genetics, epidemiology, and cognitive neuroscience. Here, I focus on the application of population neuroscience in studies of brain development. By describing in some detail four existing large-scale magnetic resonance (MR) imaging studies of typically developing children and adolescents, I provide an overview of their design, including population sampling and recruitment, assessments of environmental and genetic “exposures,” and measurements of brain and behavior “outcomes.” I then discuss challenges faced by investigators carrying out such MR-based studies, including quality assurance, quality control and intersite coordination, and provide a brief overview of the achievements made so far. I conclude by outlining future directions vis-à-vis population neuroscience, such as design strategies that can be used to evaluate the presence of absence of causality in associations discovered by observational studies. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc.