The host response to biomaterials is almost always the formation of a fibrous capsule. After implantation of a biomaterial, the body tries to heal the wound by sequentially causing acute inflammation, granulation tissue and the foreign body response, encapsulation by fibrous tissue, and capsular contracture. These responses are detrimental to many applications of biomaterials. Fibrosis is initiated by surface properties, mechanical signals, and changes in microenvironment. In fibrotic disease, there are many cells that contribute neutrophils, mast cells, macrophages, foreign body giant cells, fibrocytes, lymphocytes, fibroblasts, and, importantly, myofibroblasts. The many mediators of fibrosis include transforming growth factor pro-fibrotic cytokines, inflammatory cytokines, morphogen pathway components, matrix degrading enzymes, chemokines, and epigenetic factors. This understanding of the process has led to biomaterial-based strategies to minimize local fibrosis, often by releasing anti-fibrotic drugs.