We discussed whether we are able to select a subgroup of patients with osteopenia having a high fracture risk, in which anti-osteoporotic drug treatment can be advocated. We concluded that in individuals in whom, based on clinical risk factors, a dual-energy x-ray absorptiometry (DXA) was performed in which osteopenia was diagnosed, anti-osteoporotic treatment should be prescribed in those patients with prevalent vertebral fractures, and in patients chronically using glucocorticoids, in a dosage of 7.5 mg per day or more. Although recent developments with regard to high-resolution imaging techniques (eg, peripheral quantitative computed tomography) seem to be promising, until now they do not provide substantial more reliable information than DXA in the prediction of fractures. We think that more data are urgently needed, since safe and effective drugs are available, but there is uncertainty to which patients with osteopenia these drugs should be prescribed.