Bone tissue engineering and in vivo bioluminescence imaging are relatively new research fields, but the latter is being used increasingly to aid the former. Investigators in such diverse fields as materials science and stem cell and molecular biology are working to improve artificial grafts to treat patients who have large defects in their bones. Various polymers and ceramics, and metals such as titanium, comprise the base structures, or scaffolds, upon which bone cells are seeded and grown. However, quantifying the success of potential replacement tissue depends not just on viewing a finished product, but also on monitoring how the scaffold materials affect subsequent tissue formation, control the release of bioactive compounds and create the proper environment for tissue growth. Increasingly, this means observing bone tissue formation — both natural and artificial — at the molecular level in small animals. According to Jan de Boer and Clemens van Blitterswijk of the University of Twente in Bilthoven and Clemens Löwik of Leiden University Medical Center, both in the Netherlands, in vivo bioluminescence imaging has great potential to provide information about the molecular interactions that occur with bone formation. In a review of noninvasive imaging of bone tissue engineering, the authors provide a summary of bioluminescence imaging techniques, focusing on the use of luciferase and its derivatives in transgenic animals. They also discuss the application of imaging techniques toward the monitoring of cell numbers and distribution across a tissue scaffold, of the differentiation of osteogenic cells, and of inflammatory, apoptotic, vasculogenetic and signal transduction processes. They note that bioluminescence imaging is constrained by two-dimensional imaging methods, which cannot resolve depth — although recently introduced three-dimensional imaging systems may address this issue — and by tissue scattering and absorption of light, which limit spatial resolution. Nonetheless, ongoing improvements in imaging equipment, luciferase reporters and software likely mean that bioluminescence imaging will strongly contribute to the understanding of the in vivo dynamics of bone tissue engineering. (Biomaterials, March 2006, pp. 1851-1858.)