Early prediction of crop yield can be an important tool for identifying promising genotypes in breeding programmes. To assess whether measurements of canopy reflectance at given stages of development could be used for yield forecasting and to identify the most appropriate indices, locations and growth stages for durum wheat yield assessment, nine field experiments, each including 20 or 25 durum wheat (Triticum turgidum L. var durum) genotypes, were carried out under a wide range of Mediterranean conditions. Canopy reflectance was recorded with a portable field spectroradiometer at several times from booting to physiological maturity, and nine indices were further derived. Grain yield was measured at harvesting. The results indicated that milk-grain stage was the most appropriate developmental stage for yield assessment. However, some indices were also sensitive to yield variations when determined at anthesis or even heading or booting. The capacity of spectral reflectance indices to forecast grain yield increased on locations that allowed genotypes to express their yield potentiality. Reflectance at 550 nm (R550), water index (WI), photochemical reflectance index (PRI), structural independent pigment index (SIPI), normalized difference vegetation index (NDVI) and simple ratio (SR) explained jointly a 95.7% of yield variability when all the experiments were analysed together, 92% being explained by R550. When regression analyses were carried out separately for each experiment, spectral reflectance indices explained from 17.3% to 65.2% of total variation in yield, and the indices that best explained differences in yield were experiment-dependent. Our data suggest that reflectance at 680 nm (R680), WI and SR may be suitable estimators of durum wheat grain yield under Mediterranean conditions, when determined at milk-grain stage.