Bone metastases are among the most difficult problems to manage in patients with lung cancer. The identification of molecular mechanisms responsible for the tropism of some lung cancer cells to the bones, using gene arrays and proteomics, could help in the earlier detection of bone metastases in these patients. Furthermore, the better understanding of the interactions between lung cancer cells and the bone marrow microenvironment that mediate the process of bone destruction should result in the development of therapeutic agents, such as recombinant human OPG, RANK-Fc, and anti-PTHrP, to treat and possibly prevent this devastating complication of lung cancer.