This chapter presents results obtained on plant virus diversity and population genetics. It illustrates how the analysis of the patterns of genome variation could be a ‘window’ through which to measure the role of the different evolutionary forces that shape plant virus populations. It also emphasizes that analysis of the representativeness of samples could help compare the diversity in different plant virus populations. Simple approaches have been presented that can be used to assess statistically the role of different mechanisms affecting plant virus populations. The development of genome exploration techniques and analytical methods for studying population genetic should allow a more precise understanding of plant virus epidemiology through the study of genomic diversity within virus populations. This strategy has, however, several inconveniences: (1) it relies on regular epidemics and for many viruses and it might not be desirable to introduce laboratory virus strains in the field; (2) these experiments only explore a limited fraction of natural epidemiological situations. An easier and less costly approach is to collect virus samples in different epidemiological situations and most studies of plant virus diversity have been performed in such a context. Consequently, few environmental parameters are controlled and analysis is rendered more complex. Based on knowledge of plant virus diversity and structure, several guidelines are provided to optimize molecular epidemiology.