Annually, 221 million tons of agro-food by-products are generated worldwide, causing diverse environmental issues due to incorrect discharge. Hot trub, spent hops, brewer’s spent grains, and brewer’s spent yeast are the by-products produced in the beer manufacturing chain. These by-products contain fibers, proteins, polyphenols, essential oils, and taste compounds, presenting high possibilities of use as alternative raw materials. In this review, we compiled the knowledge gaps of brewing by-product reuse, from phytochemical compound extractions to concentration approaches, mainly concerning bitter acids and polyphenols. Moreover, we assessed and discussed the emerging technologies and alternative solvents that have allowed for higher extraction yields. We illustrated the importance of purification and concentration steps of non-destructive methods for added value in products from reuse approaches. Finally, we showed the relevance of scale-up and economic feasibility studies in order to encourage the implementation of facilities that produce bitter acids and polyphenols from alternative sources such as hot trub and spent hops.