A curative treatment for Crohn’s disease (CD) is not available, and the question of disease prognosis is primarily a question of how patients are doing in the long-term—as compared to nonaffected individuals of same age and gender—with regard to the risk of putative disease complications such as cancer and death. The disease course in CD varies from patient to patient and between years of observation, with an average of 55% being in clinical remission, 15% experiencing low activity, and 30% suffering from high disease activity in a given year during follow-up.1 It is therefore essential that the question of prognosis is assessed in true population-based patient settings representing all variants of the disease (both in terms of disease activity and disease extent), rather than in referral center populations or in surgical series representing the more severely ill part of the patient population. If study populations are selected, the derived prognostic findings cannot be used for the general information of newly diagnosed patients in whom the course of the disease is yet unknown. In the 1960s and 1970s, Truelove and Pena2 conducted the first epidemiological studies of prognosis of inflammatory bowel disease (IBD). They distinguished between prognosis in “new cases” (patients who were both diagnosed and treated in a regional hospital) and in “referred cases” (patients referred to the same hospital for treatment). The authors found that survival after 10 years of disease duration was better in regional cases (SMR, standardized mortality ratio, observed/ expected deaths, 2.3) than in referred cases (SMR, 4.9). Subsequent population-based studies have shown that mortality in patients with CD varies from being unaffected3,4 to slightly increased.5–8 The observed increase in mortality is related to extent of disease,3 female gender,5 and disease duration.5 The increase is primarily explained by an increased risk of dying from CD itself, from other gastrointestinal, liver, and biliary diseases,5–7 and from pulmonary cancer.6 The latter finding is assumingly related to the high prevalence of smokers among patients with CD.6 The disease-related mortality in CD accounts for 30% of all deaths in these patients.4,5 It can roughly be divided into clinical and/or surgical complications occurring early in the disease course, and intestinal cancer occurring later on. It remains to be investigated whether the introduction of immunomodulating/biological medications have altered overall mortality and/or causes of death in patients with CD. This possible reduction in mortality might occur from diminishing surgery rates and thereby postoperative mortality. Such changes may, however, be counterweighted by an increased risk of dying from adverse effects of medical treatment.9 The risk of intestinal cancer in CD has been assessed in a meta-analysis of 6 cohort studies from Europe, North America, and Israel.10 The reported SIRs (standardized incidence ratio, observed/expected cases) of colorectal cancer varied from 0.9 to 2.2 in the 6 studies. The overall pooled estimate was significantly increased (SIR, 1.9; 95% confidence interval [CI], 1.4–2.5). The excess risk was primarily related to an increased risk of colon cancer (SIR, 2.5; 95% CI, 1.7–3.5), but also to a nonsignificantly increased risk of rectal cancer (SIR, 1.4; 95% CI, 0.8–2.6).10 The risk of small bowel cancer in CD was assessed in the same meta-analysis and was found to be 27-fold increased (95% CI, 15–49).10 However, one should remember that small bowel cancer is a very rare condition in the background population, and that only a few observed cases result in these worryingly high risk estimates. Population-based studies have shown that patients with CD are not, as formerly suggested, at increased risk of developing lymphoma,11,12 but may be at increased risk of developing skin11,13 and pulmonary cancer.6,13 As for mortality, prospective studies of contemporary population-based CD cohorts will have to address the impact of new biological treatments on the risk of intestinal and extraintestinal cancers in these patients.