Personality neuroscience is the study of persistent psychological individual differences, typically in the general population, using neuroscientific methods. It has the potential to shed light on the neurobiological mechanisms underlying individual differences and their manifestation in ongoing behavior and experience. The field was inaugurated many decades ago, yet has only really gained momentum in the last two, as suitable technologies have become widely available. Personality neuroscience employs a broad range of methods, including molecular genetics, pharmacological assays or manipulations, electroencephalography, and various neuroimaging modalities, such as magnetic resonance imaging and positron emission tomography. Although exciting progress is being made in this young field, much remains unknown. In this brief review, we discuss discoveries that have been made, methodological challenges and advances, and important questions that remain to be answered. We also discuss best practices for personality neuroscience research and promising future directions for the field.