As the world population ages, oncologists are increasingly confronted with the problem of comorbidity in cancer patients. This has stemmed an increasing interest into approaching comorbidity in a systematic way, in order to integrate it in treatment decisions. So far, data on the subject have been widely scattered through the medical literature. This article is aimed at reviewing the available data on the interaction of comorbidity and prognosis. This overview should provide an accessible source of references for oncological investigators developing research in the field. Various methods have been used to sum comorbidity. However, a major effort remains to be done to analyze how various diseases combine in influencing prognosis. The main end-point explored so far is mortality, with which comorbidity globally is reliably correlated. A largely open challenge remains to correlate comorbidity with treatment tolerance, and functional and quality of life outcomes, as well as to integrate it in clinical decision-making.