At present, Lolland-Falster, a provincial-rural area in south-eastern Denmark, has the lowest life expectancy nationwide; about 78.6 years. This review summarises the development in mortality in this region. Mortality data from 1968 to 2017 showed this to be a new phenomenon. Until 1990, mortality in Lolland-Falster resembled the of Denmark as a whole. In the period 2013-2017, however, men in Lolland-Falster had a 15-25% excess mortality. In-migration contributed substantially to this development, since in-migrating people of working age in 2008-2017 had a 134% excess mortality. Prevention of excess mortality in Lolland-Falster requires a national effort.