Bone marrow (BM) contains hematopoietic stem cells, which differentiate into all mature blood cells, and marrow stromal cells that provide the microenvironment for hematopoietic stem/progenitor cells along with the capability to differentiate into mature cells of multiple mesenchymal tissues including fat, bone, and cartilage. Recent studies indicate that adult BM also contains cells that can differentiate into nonhematopoietic cells of ectodermal, mesodermal, and endodermal tissues other than hematopoietic tissues, including liver, pancreas, kidney, lung, skin, gastrointestinal tract, heart, skeletal muscles, and neural tissues. Studies reporting the multipotentiality of BM cells have become a focus of interest because they suggest that clinical applications could be at hand using easily obtainable cells in the treatment of tissue damage or degenerative diseases. Presently, however, definitive evidence explaining the mechanism of this multipotentiality of BM stem cells is lacking. In this review, we summarize recent progress and controversies in investigation of the multipotentiality of adult BM-derived stem cells to differentiate into nonhematopoietic tissues.