Watermelon is a speciality fruit-vegetable of the family Cucurbitaceae. The crop is widely grown in the tropics and subtropics of the globe for its mature fruits and seeds, which are excellent sources of carotenoids, flavonoids, minerals, phenolic compounds, vitamin C and the non-essential amino acid citrulline. Thus, watermelon is also regarded as a functional food owing to its capacity to prevent chronic diseases in the human body. The presence of appreciable heterosis, comparatively lower seed rate and a large number of seeds per successful cross paves the way for the development of hybrid varieties that are commercially viable. However, the commercial production of hybrid seeds is mostly carried out by manual methods, which adds extra cost. In this context, the deployment of genetically controlled pollination mechanisms like male sterility can bring down the production cost of hybrid seeds while maintaining genetic purity. Thus, this chapter focuses on different aspects of male sterility, such as its evolutionary significance, its types, the molecular mechanisms in understanding the phenomenon, the advances in omics for its thorough understanding, and the approaches for its induction, along with the present status and challenges for its utilization in watermelon improvement.