Drought stress is an inevitable factor that disturbs the production of plants by altering
morphological, physiological, biochemical, and molecular functions. Breeding for drought tolerance
requires a complete understanding of the molecular factors controlling stress-responsive pathways.
The plant responds to drought stress by adopting four mechanisms: avoidance, escape, tolerance, and
recovery. Traditional plant-breeding tools have been employed to increase tolerance in cotton, but the
complexity of drought tolerance has limited the use of these breeding methods. The plant adopts
several key strategies against drought stress, such as activating the signaling network and activating
molecular factors. Cotton breeders have been engaged in elucidating the molecular mechanisms of
drought tolerance in cotton using significant molecular tools such as quantitative trait loci (QTL)
mapping, transcription factor (TFs) analysis, transcriptome analysis, genome-wide association studies
(GWAS), genetic engineering, and CRISPR/Cas9. Breeders have studied the functional description of
genes and the interacting pathways accountable for controlling drought tolerance in cotton. Hundreds
of genes/QTL have been identified, and many have been cloned for drought tolerance in cotton;
however, a complete understanding of these traits still needs more study. This review presents a
detailed overview of molecular tools, their application for improving drought tolerance in cotton,
and their prospects. This review will help future researchers to conduct further studies to develop
drought-tolerant cotton genotypes that can thrive under conditions of water scarcity.