Tissue engineering and regenerative medicine are pursuing clinical valid solutions to repair and restore function of damaged tissues or organs. This can be achieved in different ways, either by promoting endogenous tissue repair or by using biomaterials or medical devices to replace damaged tissues. The understanding of the interactions of the immune system with biomaterials and how immune cells participate in the process of wound healing are critical for the development of successful solutions. Until recently, it was thought that neutrophils participate only in the initial steps of an acute inflammatory response with the role of eliminating pathogenic agents. However, the appreciation that upon activation the longevity of neutrophils is highly increased and the fact that neutrophils are highly plastic cells and can polarize into different phenotypes led to the discovery of new and important actions of neutrophils. In this review, we focus on the roles of neutrophils in the resolution of the inflammatory response, in biomaterial–tissue integration and in the subsequent tissue repair/regeneration. We also discuss the potential of neutrophils for biomaterial-based immunomodulation.