Biomaterials are required to act harmoniously when exposed to the body or bodily fluids. Investigating cellular or in vivo phenotypic responses and protein adsorption to the material surface helps to determine the associated biocompatibility. Past limitations on progress in this field include time-consuming cell-based screening tools and a limited understanding of the complex nature of cellebiomaterial interactions. While high-throughput technologies by their nature are a rapid tool to derive meaning from multifaceted systems and, in recent years, the biomaterial community is beginning to take advantage of these technologies, the key observation in this Leading Opinion Paper is that the biomaterials community has been slow to accept these methods as an addition to their traditional experimentation workflow. The purpose of this paper is to review the definition and recent usage of high-throughput experiments in order to examine biomaterial interactions at the cellular and wider host level, especially as they become more relevant within the biomaterials arena encapsulating tissue engineering, gene, drug and stem cell delivery systems. The technologies under focus include rapid cell-based screening, transcriptomics and proteomics.