Advanced age is associated with a higher burden of illness. Nevertheless, elderly patients suffering from internal diseases are underrepresented in clinical trials; patient, physician and protocol-designed barriers in particular prevent the recruitment of older patients with impaired medical fitness (co-morbidity, co-medication, poor performance status, cognitive dysfunction etc.). Recommendations that are based on trials in younger subjects mostly cannot be generally adopted for the elderly. Treatment in clinical practice and clinical trials should be fitness-adapted rather than age-adjusted. Normally, standard regimens are effective and well tolerated in medically fit patients of advanced age. In contrast, it may be necessary to apply modified regimens for the medically unfit. Trials exploring novel treatment modalities in the young should always allow the inclusion of elderly patients with good medical fitness. The benefit of modifying a treatment regimen in medically unfit patients of advanced age has to be determined by separate trials.