In the face of escalating global food security challenges exacerbated by climate change and evolving plant pathogens, molecular markers have emerged as pivotal tools in the development of disease-resistant crop varieties. This chapter provides a comprehensive overview of the transformative role of molecular markers in enhancing disease resistance in crops. The chapter begins by introducing molecular markers, their types, historical development, and advantages in plant breeding. It then explores the various applications of molecular markers in plant disease resistance, including marker-assisted selection, quantitative trait loci mapping, gene pyramiding for durable resistance, genomic selection, and gene editing. Furthermore, the chapter examines the practical implementation of these technologies through detailed case studies of molecular marker-assisted breeding for identifying disease resistance in chickpea, soybean, and common bean. In addition, it briefly discusses faba bean as a complex species with a recently sequenced genome. These examples elucidate the application of molecular breeding approaches in crops that contribute significantly to sustainable agriculture and global nutrition, while also expanding the scope of discussion to encompass a diverse range of plant species beyond traditionally well-studied cereal systems. The latter part examines challenges in molecular marker development, such as genomic complexity and limited genetic diversity, using faba bean as an example of a complex legume genome. Overall, this chapter provides a comprehensive overview of how molecular markers are accelerating the development of disease-resistant crop varieties to enhance global food security.