Understanding traditional hunter-gatherer lifestyles in our modern world is fundamental to our understanding of their viability, as well as the role of humans as predators in structuring ecosystems. Here, we examine the factors that drive prey preferences of modern hunter-gatherer people by reviewing 85 published studies from 161 tropical, temperate and boreal sites across five continents. From these studies, we estimated Jacobs' selectivity index values (D) for 2243 species/spatiotemporal records representing 504 species from 42 vertebrate orders based on a sample size of 799,072 kill records (median = 259). Hunter-gatherers preferentially hunted 11 large-bodied, riskier species, and were capable of capturing species ranging from 0.6 to 535.3 kg, but avoided those smaller than 2.5 kg. Human prey preferences were driven by whether prey were arboreal or terrestrial, the threats the prey afforded hunters, and prey body mass. Variation in the size of prey species pursued by hunter-gatherers across each continent is a reflection of the local size spectrum of available prey, and historical or prehistorical prey depletion during the Holocene. The nature of human subsistence hunting reflects the ability to use a range of weapons and techniques to capture food, and the prey deficient wildlands where people living traditional lifestyles persist.