Underutilized crops do not benefit from the same research effort as major crops even if they are locally essential for food security. Knowledge and resources developed on major crops could be transferred to the lesser studied ones in order to analyze and exploit the genetic and agronomical potential of these crops. Fonio, so-called by farmers and consumers, includes Digitaria exilis Stapf. and D. iburua Stapf. as well as wild related species (D. ternata and D. longiflora) and Brachiaria or Panicum genera. It is an indigenous staple crop in western Africa regarded as a valuable source of income, especially for small scale farmers. Recent progress in post-harvest technologies, which has long hampered the development of fonio cultivation, has increased its economic potential. The need to characterize its genetic resources and adaptive potential to the changing climate, and more generally, fast evolving environmental pressures, is therefore more important. We shall discuss how the study, conservation and uses of fonio genetic resources can take advantage of methodological advances in other plant genetic research. Several issues are addressed, which are not only related to biotechnologies but also to the combination of biological and social science approaches. The genetic structure of crop on-farm diversity results from the interplay between numerous factors, including historical, social, cultural, economic, biological and environmental factors. Molecular resources can now be developed rapidly. Combined with innovative and multidisciplinary approaches, this will lead to an accurate estimation of fonio evolutionary history (including domestication), as well as an evaluation of the genetic resources and their dynamics. These approaches will allow a better understanding of on-farm diversity of fonio, the development of sound collecting and ex situ conservation strategies and appropriate crop improvement to ensure food security.