Remarkable parallels link the development of varietal mixtures across subsistence farming systems. Mixtures are grown and persist because they prolong harvest and income flow and provide diversity of diet. From our review of research on agronomic and disease aspects of mixtures in modern agriculture, it is also clear that improved stability and decreased disease severity are common features of mixtures relative to their components in monoculture. Such advantages are of value to both modern and subsistence agriculture. However, in the majority of cases, the yield advantage of mixtures is small. Overall, we conclude that varietal mixtures are presently a viable strategy for sustainable productivity in subsistence agriculture, have potential for improvement without sacrifice of diversity, are an important resource for future global food production and may have an expanding role in modern agriculture in situations where qualitative uniformity is not the guiding priority.