Durum wheat is a major crop grown in Mediterranean regions. Its grain characteristics including high protein content and yellow pigmentation make it unique for many end products such as pasta and couscous. Under rainfed environments, combined stress episodes of water deficiency and high temperatures during reproduction often severely limit grain yield and quality. Improving crop production under stressful environments has become a pressing challenge for researchers and breeding programs. Consequently, understanding the mechanisms which contribute to crop reproductive success is of the highest priority. Epigenetic mechanisms have emerged as a powerful regulatory system to control gene expression and biological processes in plants, showing great potential for molecular breeding and crop improvement. Our research focuses on: 1) evaluating the genotypic diversity in Australian durum germplasm in response to single and combined pre-anthesis water-deficit stress and post-anthesis heat stress; 2) discovering the small RNAs (sRNAs) that control grain development and quality under different stress; and 3) analysing their expression dynamics across superior and inferior durum genotypes during grain development. We have detected significant genotypic differences in stress response by evaluating physiological activities, morphological traits, developmental events and most importantly, yield components and grain quality parameters. Contrasting sensitivity of production and quality traits to different reproductive-stage stresses was confirmed in the Australian varieties and breeding lines studied. Small RNA expression profiling was performed in the stress-tolerant and -sensitive genotypes at different developmental stages during reproduction. We identified durum sRNAs with contrasting expression patterns under single and combined stresses, specific to the grain developmental stage and genotype. We will discuss key sRNA-target modules that regulate grain development under stress, contributing to the differences in durum germplasm performance.