In the field of animal nutrition, butyrate is used as a zootechnical ingredient and can be used as an unprotected salt or in the form of protected derivatives such as butyrate glycerides or butyrate-loaded matrices. Dietary butyrate supplementation has been shown to improve growth performance and resilience of broiler chickens through distinct mechanisms, operating on both eukaryotic and prokaryotic cells. Firstly, butyrate influences endogenous avian cells in multiple ways: it is an agonist of free-fatty acid receptors, an inhibitor of pro-inflammatory pathways, an epigenetic modulating agent and acts as an energy source. Secondly, butyrate influences the microbiota residing in the avian gastrointestinal tract (GIT) as a result of its bacteriostatic properties. The responses, e.g. changes in growth performance, gut morphology, carcass traits or nutrient digestibility of chickens, to dietary butyrate supplementation are inconsistent with factors such as additive inclusion level, diet composition, age and health status of the bird modulating the effects of butyrate and its derivatives. For many derivatives, the precise GIT segment wherein butyrate is released is unclear. Release location may affect the observed responses to butyrate given the diversity of cell types and pH conditions encountered throughout the gastrointestinal tract of poultry, and the differences in microbiota composition in the different gut segments. As a consequence, our understanding of the mode of action of butyrate is hampered. Characterisation of existing derivatives and development of targeted-release formulations are, therefore, important to gain insight in the different physiological effects butyrate can elicit in broiler chickens.