Indian melon (Cucumis melo L.) landraces comprise a wealth of genetic diversity that has been exploited over the millennia by farmers and over the last century by scientifically trained plant scientists in the public and private sectors. Melons in India may be feral or cultivated, have netted or smooth rinds, be sweet and eaten as a dessert fruit or not sweet and consumed as a vegetable fresh, cooked, or dried. The fruit may be processed for sweet juice and confectionary flavoring, and the seeds are a source of high-quality cooking oil and high-protein seed meal. This chapter reviews genetic variation for resistance to fungal, bacterial, and viral diseases and to nematodes and insects; and tolerance to soil salinity, drought, flooding, and high temperatures with a focus on melon accessions of Indian origins. Some of these resistances have knowing or unknowingly been transferred through scientifically based breeding programs into open-pollinated and hybrid sweet melon cultivars grown in Africa, Asia, Australia, Europe, and the Americas for domestic and export markets. Indian melons include unique sources of high acidity and sugar: acid ratio that enable breeding for new combinations of sweet and sour flavors for fresh and processed melon products. Genetic variation in carotenoids (b-carotene), ascorbic acid, and micronutrient (Fe and Zn) contents in Indian germplasm promise more nutritious melons. High percentages of unique alleles are present in southern (24.2%)andeastern (30.4%) Indian landraces and in ‘‘wild’’ accessions from northern India (34.5%). Extensive collection, preservation, and evaluation of Indian melon landraces is vital to prevent further genetic erosion in this primary center of melon diversity, to increase genetic variability for melon breeding, and to introduce new traits into modern melon cultivars. International collaborations are developing genomics tools for melon that will facilitate allele mining within Indian germplasm and introduce new genetic variability. We are on the verge of an exciting era of melon genetic improvement as whole-plant breeding and genomics technologies combine to preserve and fully characterize the complete array of genetic variability in melon and exploit that germplasm and information for the further improvement of salad and dessert melons for diverse markets worldwide.