Display omitted •Description of cocoa production chain and residual biomass generation.•Cocoa by-products as a source of high-value-added molecules.•Biotechnology as an alternative for the biotransformation of cocoa by-products.•Relevance of sustainability, innovation and technology in cocoa industry. Cocoa beans provide raw materials for global food industries valued in excess of $47 billion in world exportations. Through on-farm processing, about 80% of cocoa fruit is discarded as residual biomass, including cocoa pod husks, cocoa bean shells and cocoa sweatings. Farmers routinely discard these residues/by-products during the initial cocoa bean processing steps, occupying vast areas and raising social and environmental concerns. Alternatively, this residual biomass is used as cocoa tree fertilizer. However, its disposal is performed without proper treatment, resulting in putrid odors and plant diseases. Recently, some studies have reported the use of cocoa by-products in the production of high-value-adding molecules with potential applications in the food, pharmaceutical and cosmetic industries. In this aspect, biotechnological approaches have been shown to be a viable alternative for the transformation of this residual biomass into fine products. This article reviews the biotechnological approaches implemented for the management and exploitation of cocoa by-product. Related topics on cocoa production and residual biomass generation, sustainability and valorization of cocoa chain are addressed and discussed.