Heterosis (or hybrid vigor) is a natural phenomenon whereby hybrid offspring of genetically diverse individuals display improved physical and functional characteristics relative to their parents. Heterosis has been increasingly applied in crop production for nearly a century, with the aim of developing more vigorous, higher yielding and better performing cultivars. In this review we present and compare three categories of crop heterosis utilization: intraspecific heterosis, intersubspecific heterosis and wide-hybridization heterosis, with particular focus on polyploid species. Different pollination-control systems used to breed for heterosis are also comparatively analyzed. Finally, we highlight problems involved in heterosis research and crop improvement. We aim to provide insight into best practices for amplifying heterosis potential.