The immune system is an important barrier for defense in the human body. This system includes B cells, T cells, dendritic cells (DC), and macrophages, which play a pivotal role in tissue injury, tumor, and bone remodeling. The understanding of macrophages has improved in the past years, but numerous mechanisms between macrophages and biomaterials remain largely unknown. Thus, the present study discusses the response between macrophages and biomaterials and predicts their potential application to provide new ideas for basic and clinical research.