Nanomaterials exhibit unique properties that are absent in the bulk material because decreasing material size leads to an exponential increase in surface area, surface area to volume ratio, and effective stiffness, resulting in altered physiochemical properties. Diverse categories of nanomaterials such as nanoparticles, nanoporous scaffolds, nanopatterned surfaces, nanofibers, and carbon nanotubes can be generated using advanced fabrication and processing techniques. These materials are being increasingly incorporated in tissue engineering scaffolds to facilitate the development of biomimetic substitutes to replace damaged tissues and organs. Long‐term success of nanomaterials in tissue engineering is contingent upon the inflammatory responses they elicit in vivo. This review seeks to summarize the recent developments in our understanding of biochemical and biophysical attributes of nanomaterials and the inflammatory responses they elicit, with a focus on strategies for nanomaterial design in tissue engineering applications. WIREs Nanomed Nanobiotechnol 2015, 7:355–370. doi: 10.1002/wnan.1320 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement