Vulnerable groups are often excluded from clinical research on the basis of scientific, ethical and practical reasons. Although intended to protect vulnerable people and maintain study integrity, exclusion of vulnerable groups from research through use of standard exclusion criteria may not always be necessary and may result in findings that are not generalisable. Achieving a balance between the competing needs to protect vulnerable people and to make progress in our understanding of disorders and their management through research requires a reconsideration of exclusion criteria and consent processes to ensure vulnerable people are appropriately represented in clinical research. Reasons for development of broad exclusion criteria include both concrete barriers and intangible discouraging factors. This paper examines this situation and its consequences, perceived and real barriers to inclusion of vulnerable people in research, and suggests methods for overcoming these barriers and applying thoughtful exclusion criteria.