When conducting in vitro research on bone, a choice has to be made between using bone organ or bone cell cultures. When one decides to use the latter, the question is whether to use primary cells or cell lines. The advantage of using cell lines over freshly isolated cells lies in the ready availability of large numbers of cells, the homogeneity of the cell cultures, and the expected invariability of the phenotype. In the long run, however, cell lines appear unstable to some extent. In addition, their clonal selection has favored rapidly growing cells, but has not necessarily selected for the whole range of bone-specific gene expression characteristic of primary bone cells. This means that in certain experiments, the use of primary bone cells is preferred to the use of cell lines.