Heterosis, or hybrid vigor, an unsolved puzzle and a ‘miraculous’ agricultural phenomenon, refers to the phenomenon in which hybrid progeny of two inbred varieties exhibits enhanced growth or agronomic performance. Converse of hybrid vigour is ‘inbreeding depression’ caused by increased homozygosity of individuals, which reduces survival and fertility of offspring. Agricultural heterosis was observed nearly 100 years ago when hybrid plants out yielded their inbred parents and today this “hybrid vigor” is a major provider for global food production. One of the most promising approaches to unravel the genetic basis for heterosis at the molecular level emerged through the availability of molecular markers, as they have provided a powerful approach to map and subsequently identify genes involved in complex traits. Molecular marker technology was used to identify the genomic regions that contribute to heterosis for a trait of interest. The advancements in functional genomics have created a novel avenue to study the genetic basis of heterosis at the gene-expression level. The genetic basis of heterosis has been debated with respect to the relative importance of dominance, overdominance and epistasis; where one of the problems has been the use of whole genome segregating populations where interactions often mask the effects of individual quantitative trait loci. In this review the phenomenon of heterosis and the modern concept of its genetic and molecular basis will be discussed.