A little more than 500 years ago, there were no European settlers in the vast lands that now constitute North America. To understand the Black health experience in English North America from 1619 to 1730, a brief digression into New World history is necessary. The tragic story of the eradication of Native American populations throughout the Western hemisphere provides a cultural foundation for exploring the European response to non-White people. An examination of Spanish, Portuguese, English, and French medical practices will place slave health status and outcomes in context.