Functionalisation of biomaterials with therapeutic moieties (proteins, drugs, genes) is a pre-requisite to tissue regeneration and restoration of function following injury or disease. However, up until now, single-factor delivery has not proven to be clinically efficacious, most likely due to the complex nature of pathological states. In this regard, strategies that respect the complex nature of disease can prove successful, paving the way for the delivery of several factors to modulate several stages of the pathology over time. Biomaterials offer opportunities to deliver multiple therapeutics in a temporal manner (multi-modal release) using a number of strategies. The importance of these strategies will be described, as well as the methodologies used to achieve multi-modal release. Furthermore, strategies to engineer more programmed and responsive biomaterials as multi-modal delivery systems will be explored.