Virgin soil epidemic is a term coined by Alfred Crosby,  defining it as epidemics "in which the populations at risk have had no previous contact with the diseases that strike them and are therefore immunologically almost defenseless". The concept is related to that developed by William McNeill in which he connected the development of agriculture and more sedentary life with the emergence of new diseases as microbes moved from domestic animals to humans.  Virgin soil epidemics have occurred with European colonization, particularly when European explorers and colonialists brought diseases to lands they seized in the Americas, Australia and Pacific Islands.  This concept would later be adopted wholesale by Jared Diamond as a central theme in his popular book Guns, Germs and Steel as an explanation for successful European expansion.
When a population has not had contact with a particular pathogen, individuals in that population have not built up any immunity to that organism, and have not received immunity passed from mother to child.  Epidemiologist Francis Black has suggested that some isolated populations may not have mixed enough to become as genetically heterogeneous as their colonizers, which would also have affected their natural immunity.  This can also happen when a considerable amount of time has passed between disease outbreaks, that no one in a particular community has ever experienced the disease to gain immunity.  Consequently when a previously unknown disease is introduced to such a population, there is an increase in the morbidity and mortality rates; historically this increase has often been devastating, and always noticeable. 
Virgin soil epidemics also occurred in other regions. For example, the Romans spread smallpox through new populations in Europe and the Middle East in the 2nd century AD, and the Mongols brought the bubonic plague to Europe and the Middle East in the 14th century. 
Research over the last few decades has questioned some aspects of the notion of virgin soil epidemics. David S. Jones has argued that the term "virgin soil" is often used to describe a genetic predisposition to disease infection, and obscures the more complex social, environmental, and biological factors that can enhance or reduce a populations susceptibility.  Paul Kelton has argued that the slave trade in Indigenous people by Europeans exacerbated the spread and virulence of smallpox and that a "Virgin Soil" model alone cannot account for the widespread disaster of the epidemic.  Cristobal Silva has re-examined accounts by colonists of 17th century New England epidemics and has explored how they were products of particular historical circumstances rather than universal or genetically inevitable processes. 
- Columbian Exchange
- Ecological imperialism
- Influx of disease in the Caribbean
- Seasoning (colonialism)
- Millenarianism in colonial societies
- Cocoliztli epidemics
- Crosby, Alfred W. (1976), "Virgin Soil Epidemics as a Factor in the Aboriginal Depopulation in America", The William and Mary Quarterly, Omohundro Institute of Early American History and Culture, 33 (2), pp. 289–299, JSTOR 1922166
- McNeill, William H. (1976), Plagues and Peoples, Anchor Press, ISBN 978-0385121224
- Cliff et al, p. 120
- Hays, p. 87
- Daschuk, James (2013). Clearing the Plains: Disease, Politics of Starvation and the Loss of Aboriginal Life. Regina: University of Regina Press. pp. 11–12. ISBN 9780889772960.
- Alchon, p. 80
- Jones, David (2003). "Virgin Soils Revisited". The William and Mary Quarterly. 60 (4): The William and Mary Quarterly.
- Kelton, Paul (2007). Epidemics and Enslavement: Biological Catastrophe in the Native Southeast, 1492-1715. Omaha: University of Nebraska Press.
- Silva, Cristobal (2011). Miraculous Plagues: An Epidemiology of Early New England Narrative. Oxford, U.K.: Oxford University Press.
- Alchon, Suzanne Austin (2003), A Pest in the Land: New World Epidemics in a Global Perspective, University of New Mexico Press, ISBN 0-8263-2871-7
- Cliff, Andrew David; Haggett, Peter; Smallman-Raynor, Matthew (2000), Island Epidemics, Oxford University Press, ISBN 0-19-828895-6
- Hays, J. N. (2005), Epidemics and Pandemics: Their Impacts on Human History, ABC-CLIO, ISBN 1-85109-658-2