Heterosis results in the phenotypic superiority of a hybrid over its parents with respect to traits such as growth rate, reproductive success and yield. This hybrid vigor is determined by non-mutually exclusive mechanisms, including dominance complementation, overdominance and epistasis. Heterotic genes responsible for elevating crop yields are now being sought using genomics, particularly transcriptomics, but with contradictory results. Because heterosis is an environmentally modified quantitative phenotype, genomic analyses alone will not suffice. Future research should focus on integrating genomic tools in a framework of comprehensive quantitative trait locus (QTL)-based phenotyping, followed by map-based cloning. This 'phenomics' approach should identify loci controlling heterotic phenotypes, and improve understanding of the role of heterosis in evolution and the domestication of crop plants.