This commentary demonstrates that ‘Geography and chronic disease’ can be associated in unique ways and may point to links in the chain of disease causation in epidemiological studies. Examples from the 1900s and 2000s evince that critical causal insights into disease were gained by utilizing opportunities provided by geography. In the 1940s, studies that investigated why some cancers were more frequent in specific geographical areas than in others have provided important etiological clues. After comparing disease incidences in Africans versus African-Americans, Kennaway suggested that environmental, rather than genetic or ethnic, factors contribute to hepatic cancers. Further clues into disease etiology were provided through the investigation of ”epidemiological islands“. One example is the discovery of ”new mechanisms for the origin and dissemination of infectious diseases,“ for which Gajdusek was honored as a colaureate of a Nobel Prize in 1976. As early as the beginning of the 1900s, scientists suggested that studies of cancer development in regions around the Earth's North Pole could be a promising research avenue. Still today, studying cancer in populations that live at extreme latitudes seems to be a promising geographic approach to better understand public health, given that two of the world's most frequent malignancies, namely breast and prostate cancer, are very rare in populations residing north of the Arctic Circle. Overall, this commentary serves as a reminder that the geographically different distribution of chronic diseases across the globe may provide unique opportunities for investigating what protects geographically confined populations against, or what makes them more susceptible to, chronic disease.