Empirical studies and ethical-legal analyses have demonstrated that incidental findings in the brain, most commonly vascular in origin, must be addressed in the current era of imaging research. The challenges, however, are substantial. The discovery and management of incidental findings vary, at minimum, by institutional setting, professional background of investigators, and the inherent differences between research and clinical protocols. In the context of human subjects protections, the challenges of disclosure of unexpected and potentially meaningful clinical information concern privacy and confidentiality, communication, and responsibility for follow-up. Risks, including a blurring of boundaries between research and clinical practice, must be weighed against the possible benefit to subjects and a moral duty to inform. Identification and examination of these challenges have been met by scientific interest and a robust, interdisciplinary response resulting in the pragmatic recommendations discussed here.