Plant interspecific F₁ hybrids sometimes are vigorous, but they also reveal sever weakness which has been known as hybrid lethality. Hybrid lethality acts as a major reproductive barrier, eventually blocks gene exchanges between species. Unavailability of interspecific hybrid progenies is an obstacle for widecrossbreeding, and requiring information on nature of hybrid lethality to improve efficiency of this breeding program. However, little is known about physiology and biochemistry of the hybrid cell death, and the genes involved in hybrid lethality are enigma. Recently, new studies started to uncover the facts about how hybrid cells die and which genes are supposed to control hybrid lethality. This article reviews up-to-date studies on hybrid lethality in plants.