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At first (i.e. immediately after the arrival of Europeans) it was imported European Infectious Diseases that the Native Americans had no immunity to (e.g. smallpox, measles, rubella, bubonic plague, chickenpox, pneumonic plague, cholera, diphtheria, influenza, scarlet fever, typhus, tuberculosis, whooping cough). Between all of these various diseases it has been estimated that as much as 90% of the original Native American population may have died, leaving much of the continents of North and South America open and unoccupied for the new European settlers (until Native American populations slowly began to recover).

Later and to the present it has been abuse of alcohol, modern commercial tobacco products, etc.

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