Relevant criteria to assess specific diseases have been heavily discussed since Rudolf Virchow when morphologic changes represented the center of interest. However, nowadays presence and severity of disease cannot exclusively depend on the mere absence or presence of morphologic criteria anymore. The progress in basic and clinical science, moral values and economic constraints imply to reflect, concretize and ultimately operationalize the goals of medical therapy. Recent advances in molecular biology and genetics have lead to further understanding of pathophysiological mechanisms of disease and opened new ways for sophisticated and individualized therapeutical approaches. It is important to reconsider the definition of health and appropriately address functional and quality of life aspects. The categorical classification of therapeutical options, i.e. curative versus palliative therapy, does not provide satisfying answers to several clinical scenarios such as early stage prostate cancer in older adults or functional limitations in patients with peripheral arterial disease. Clinical research does acknowledge increasingly that relevant outcomes extend well beyond the quantitative prolongation of life. The scientific field of health services research is supposed to increase the evidence base of these decisions. Lastly, the goals of therapy should not be defined by physicians alone. It is important to inform the patient appropriately and discuss individual prognosis, therapeutical options and goals. Ultimately, therapy should be based on a shared decision making process.