Heat stress is a significant threat that limits crop yield and fecundity all over the world. Prevalent strategies for heat adaptation that alter technical and management systems are inadequate to sustain yield. As such, the identification of heat-tolerant genotypes with improved yield potential is crucial. Raising tolerant and stable cultivars can be tedious as heat-stress responses are highly variable across different developmental stages. While molecular breeding has progressed in engineering heat-tolerant lines, the complexity of genetic networks and divergence of heat tolerance mechanisms is the main hindrance for plant breeders. Hence, insight into the physiological and reproductive traits associated with heat tolerance could assist in the development of strategies to screen germplasm for heat tolerance. Exploitation and use of landraces and wild relatives in breeding may enhance favorable genetic diversity in crop plants. A holistic approach to delineate molecular markers, where quantitative trait loci (QTLs) for different traits linked to heat tolerance involving physiological and reproductive traits are characterized in well-controlled field environments, may be an option for optimizing germplasm under heat stress. Here, we present an outline of the effects of heat stress and its associated tolerance mechanisms in food crops, along with some physiological, molecular and reproductive characteristics such as ‘stay-green,’ membrane thermostability, canopy temperature depression, metabolites, genes, QTLs, and pollen fertility. Further, we provide information on conventional and molecular breeding approaches as well as different selection strategies for heat stress tolerance.