Sesame, the queen of oilseed crops, exhibits drought tolerance and has evolved to thrive in dry tracts. It is susceptible to waterlogging; even two to three days of waterlogging results in a sharp decline in yield. Evolving waterlogging-tolerant sesame varieties is the most cost-effective approach to sustain sesame production under changing climatic conditions. Breeding for waterlogging tolerance in sesame is gaining momentum due to its significant impact on crop yield and quality. Recent studies have identified genotypes with varying tolerance levels, highlighting the importance of genetic diversity and selection methods. In conventional breeding, the selection of waterlogging-tolerant genotypes is an important step. No standard screening procedures are available to identify waterlogging-tolerant genotypes in sesame. High throughput screening techniques that combine fully automated robotic systems for imaging and data processing are required for in-depth research. Though appreciable improvement has been made in genomics and candidate genes / QTLs identified for waterlogging tolerance in sesame, integration of traditional breeding with molecular techniques is lacking. A multidisciplinary approach is required to develop waterlogging-tolerant sesame varieties. In this mini-review, an attempt has been made to document the physiological, morphological and biochemical response of sesame to waterlogging and the challenges of screening and breeding sesame cultivars that are tolerant to waterlogging.