In all cases, European settlers relied on the aid of Native American initially to survive and establish colonies. In all cases, increasing friction led to hostilities which led to war and eventual colonial victory.

In Jamestown (Opechanacanough), conflict was spurred by an ever increasing number of colonists being pushed west by the need for fresh land for tobacco. Additionally, many of these settlers took the best land along the navigable waterways. In 1622, the Powhatans led by Opechanacanough, killed abut 1/3 of the settlers in Virginia but suffered devastating repercussions. In the 3rd Powhatan War, 1644, Opechanacanough was captured and killed, signaling the end of Powhatan resistance.

The Pequot War (1634-1638) was an alliance of New Englanders along with the Narangansett and Mohegan fighting the Pequot. Conflict was fueled by both colonial encroachment and native competition in the fur trade. Most important from the Pequot War was the brutal colonial massacre of an estimated 700 defenseless women and children at Mystic River (1638).

King Philips' War (1675-1678) was precipitated by colonists encroaching on land and economic rivalries with the Iroquois. Although King Philip's alliance was initially successful, attacking more than 100 colonial settlements, they were eventually defeated.

The Pueblo Revolt (1680) was led by Pope' and focused primarily on the Spanish contempt for native culture and forcing indigenous peoples to convert to Roman Catholicism. The Pueblo Revolt drove the Spanish out of present day New Mexico for over a decade.

Pontiac's Rebellion (1763) was a post French and Indian War attempt to stop colonial westward encroachment on native lands. Led by the Ottawa chief Pontiac, natives scored early victories before an eventual negotiated peace with the British. The result was the Proclamation Line of 1763 which, generally, barred colonists from moving west of the Appalachian Mountains. Colonists wee incensed by the British taking away possible land which they believed that they had fought for during the French and Indian War. This attempt at racial segregation by legal declaration along a geographical line failed. This failure would be repeated.

Brown also attempted to obtain the guns from a federal arsenal at Harper's Ferry to start and arm a slave rebellion. Although unsuccessful and eventually hanged for conspiracy and treason, Brown became a pivotal figure in defining the irrepressible conflict looming between the North and the South.

In the North, Brown was seen as a martyr for a noble cause. In the South, Brown was seen as a blood thirsty murderer, one of many radical abolitionists ready to arm slaves to wage war against slave holding states.