Downy mildew, caused by Sclerospora graminicola, is the most damaging fungal disease of pearl millet in Africa and Asia. In India, new single-cross hybrid cultivars have been withdrawn following epidemics that occurred when pathogens that could overcome resistance genes deployed in these genetically uniform cultivars became common. Resulting yield losses were heavy. S. graminicola populations maintain haplotype variation through extensive sexual reproduction, making the breeding of single-cross hybrids with durable resistance difficult. Nonetheless, cultivation of adapted, high-yielding, disease-resistant crop cultivars continues to be the most economical method of disease control. When resistant cultivars are unavailable, the use of metalaxyl as a pre-planting seed treatment provides protection for a limited time. Roguing infected plants in the field can reduce production of primary inoculum for the following pearl millet crop. Research priorities for the new millennium should include elucidation of the genetics of pathogen virulence and the development and deployment of cultivars with durable resistance. Marker-assisted selection is a promising new tool that will permit development of agronomically uniform pearl millet cultivars that are heterogeneous for downy mildew resistance. However, if agronomic uniformity is not essential, then topcross hybrids and three-way hybrids should provide more durable resistance while still providing the benefits of hybrid vigor and satisfying the desire of seed producers and distributors for a high seed replacement rate.