Sesame ( Sesamum indicum L.) is the oldest important edible oilseed crop found throughout many tropical and subtropical regions of the world. India ranks second in its domestication with a total production of 0.67 million tons. The growth index of sesame in Asia, Africa, and South and Central America is 54.9%, 40.8%, and 4.3%, respectively. The crop has high economic potential but stress factors like temperature sensitivity, early senescence, pest attack, water logging, and disease infestations limit its productivity worldwide. Its recalcitrant nature, sexual incompatibility, and post fertilization barriers greatly restrict the generation of new varieties, via tissue culture and traditional breeding strategies. Thus, genetic engineering appears to be the best alternative to improve its yield by developing stress-tolerant plants. The callus induction and regeneration frequency in sesame is highly genotype dependent. Regeneration is observed in different cultivars via callus phase or directly from different explants mainly on Murashige and Skoog basal medium (MS) with high cytokinin and low auxin concentrations. The attempts towards developing genetic transformation protocols has resulted in very limited success. The present review highlights the history and discusses the detailed progress of sesame tissue culture and genetic transformation research with respect to genotype dependency, different medium compositions, plant hormones, and explant age.