Sesame (Sesamum indicum L.) is one of the world's oldest oil crops and has been cultivated in Asia from ancient times. India has a rich diversity of this crop and a landrace collection is maintained at the National Genebank at the National Bureau of Plant Genetic Resources (NBPGR). The breeding potential of this germplasm has been hardly exploited to date. The major hindrance for the utilization of these resources is the transfer of diversity into a form that can be easily used by breeders and farmers. As part of a core collection strategy, a selection was made of 24 of the most diverse and unadapted parental lines, including one accession of the wild species S. mulayanum, and these were intercrossed in various combinations to maximize genetic diversity and to develop locally adapted pools of genetic resources. A weak and decentralized selection regime was maintained at four selected target sites on the progeny of 103 crosses. The range of variation in the selected F4 progenies was assessed, and promising types with desired plant characteristics and high seed yield were selected. Realized genetic gains, especially for yield-related traits, were also assessed. Only a limited fraction of the existing diversity held in the genebank was used in the present study and there is much more diversity available for large-scale genetic enhancement of sesame in the future.