Hybrid-enabled line profiling (HELP) is a new integrated breeding strategy for self-fertilizing crops that combines existing and recently identified elements, resulting in a strategy that synergistically exceeds existing breeding concepts. Heterosis in selfing crops is often driven by additive and additive × additive gene action, the molecular basis of which is increasingly being revealed. Unlike nonadditive heterosis, additive forms can be relatively easily fixed in homozygous lines, meaning that their seed can simply be resown to express the same “heterosis.” Crossing diverse, complementary “selfing” parents to create the desired trait or allele line profile requires strict male sterility of the female; this can now be achieved relatively easily through present and emerging chemical, environmental, or genetic techniques. Fairly small amounts of hybrid seed are needed, with no need to scale up seed production, as it is not the hybrid that will be commercialized. After multilocation testing, homozygous lines from only the most superior hybrids, driven mainly by additive effects and additive × additive gene action, are rapidly derived using techniques such as doubled haploids. Multilocation testing and molecular confirmation of target line profiles then identify superior lines for release to farmers. The HELP strategy integrates modern high-throughput versions of existing and new concepts and methodologies into a breeding system strategy that focuses on the most superior crosses, < 10% of all crosses. This focus results in significant increases in efficiency and can reverse the edible yield plateauing seen or feared in some of our major selfing food crops.