Homocysteine is a metabolic intermediate in the methionine-cysteine conversion. High level of homocysteine in blood leads to changes in methylation pathways and consequently in transcriptional activation; therefore, it can disrupt gene expression. This chapter presents the biochemical pathways of the transformation of homocysteine in broilers and demonstrates the beneficial effects of certain bioactive feed additives (betaine and berberine) to health-related and production problems caused by the accumulation of homocysteine. Based on recent scientific findings, the following conclusions have been drawn: Hyperhomocysteinosis has received little attention in the field of avian physiology research. Currently used feed additives, such as betaine, potentially decrease circulating homocysteine, but support only one of the pathways responsible for homocysteine decomposition. Various phytonutrients may be suitable owing to their pleiotropic bioactive components, such as berberine. It can potentially maintain redox homeostasis in animals and modulate immune responses and therefore may be able to provide for liver protective functions. Additionally, it can encourage healthy tissue to express enzymes that are responsible for the degradation of homocysteine. Further studies are recommended to investigate how effectively berberine can reduce the incidence of hyperhomocysteinemia in broilers and whether it is necessary to use feed supplements throughout the life cycles of birds.