As was true 10 years ago, tremendous interest surrounds the concept of "bone quality," as shown by the intense and growing research activity in the field. The urgency to advance knowledge in this area is motivated by the need to understand not only the causes of increased skeletal fragility with aging and disease, but also the mechanisms by which drugs reduce fracture risk. As reflected in the preceding articles, in the past decade collaborations between biologists, physicists, engineers and clinicians have led to new insights regarding the biological, material and structural features that contribute to skeletal fragility. Despite these new insights, important issues remain unresolved. Our challenges lie in identifying, describing and understanding the totality of features and characteristics that determine a bone's ability to resist fracture, and using this information to identify new therapeutic targets and develop better biomarkers and noninvasive imaging modalities. This summary is intended to integrate reports in the literature with presentations and discussions that occurred during the meeting, to highlight areas of consensus and those of continued controversy, and thus to identify critical areas for future research.