Rapidly evolving advances in wound-care technologies and treatment modalities, including locally injectable granulocyte-macrophage colony-stimulating factor (GM-CSF), are increasingly being used. Based on its role in the stimulation and recruitment of key contributors to wound healing, such as keratinocytes, macrophages, and fibroblasts, GM-CSF is considered to play an essential role in the wound-healing cascade. Synthetic GM-CSF has been shown to have a positive effect on the healing of chronic wounds when given as a local injection in a small number of patients. Subsequent randomized, controlled trials demonstrated that GM-CSF accelerated the healing of chronic wounds. This paper reviews the proposed mechanism of action of GM-CSF in wound healing. We also describe its method of application in the operating room at a tertiary care center for patients with wounds. Key Messages: Many types of chronic wounds have an altered keratinocyte and macrophage function that can be potentially assuaged by the addition of locally injected growth factor therapy to standard-of-care treatment. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to be beneficial for the treatment of chronic, non-healing wounds. This article reviews the data on GM-CSF, reports a proposed mechanism of action, and describes its use by a team of wound surgeons.