The book is illustrated with monochrome reproductions of historic depictions of the exchange, such as of "King Ferdinand looks out across the Atlantic as Columbus lands in the West Indies", and with maps such as of the distributions of blood group genes in the world's aboriginal populations.

[1] G. S. Dunbar called Crosby's work a "lively little book", noting his invention of the term "biohistory", and the reluctance of historians to explore that field, which lay somewhat outside "their traditional literary education".

[2] Wayne D. Rasmussen wrote that farmers are well aware of the pests and diseases that follow cultural and biological exchanges.

[3] Frederick Liers wrote in 2005 that Crosby had difficulty getting the book published, and that when he did, conventional historians paid it little attention.

[4] In the foreword to the 2003 edition of the book, J. R. McNeill says that in 1972 "Crosby's ideas met with indifference from most historians, neglect from many publishers, and hostility from at least some reviewers, (but) they now figure prominently in conventional presentations of modern history.