Growth factors and cytokines play a crucial role in wound healing, with several being used clinically for non-healing wounds such as pressure ulcers, chronic venous ulcers, and diabetic foot ulcers. This review discusses four key growth factors and cytokines: granulocyte-macrophage colony stimulating factor (GM-CSF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF). While clinical results are encouraging, many studies have small sample sizes and varied endpoints, necessitating further research for definitive evidence of efficacy. GM-CSF, a cytokine present in wound beds, promotes wound healing by enhancing myofibroblast differentiation, inflammatory cell recruitment, and epidermal proliferation. It has been approved for use in certain clinical settings, with studies showing improved healing in chronic venous ulcers. However, its use is associated with minimal side effects. PDGF, involved in all stages of wound healing, has been shown to accelerate wound closure in diabetic foot ulcers. Becaplermin, a recombinant PDGF, has been approved for use in chronic venous ulcers but is associated with potential malignancy risks. bFGF promotes granulation tissue formation and re-epithelialization, with studies showing improved healing in pressure ulcers. VEGF is important for angiogenesis and has been used in treating diabetic wounds, though its efficacy in chronic venous ulcers is less established. Despite promising results, the use of these growth factors is limited by small study sizes, varied endpoints, and the need for larger randomized controlled trials. Additionally, the harsh environment of chronic wounds, characterized by protease activity and imbalanced collagenolytic activity, poses challenges for effective growth factor delivery. Debridement is essential to remove non-healing tissue and create a suitable microenvironment for growth factor activity. While exogenous growth factors show potential, their use should be combined with standard of care treatments and evaluated for safety and efficacy in future studies. The role of protease inhibitors in conjunction with debridement is also being explored to enhance growth factor activity in chronic wounds. Overall, growth factors and cytokines are essential for wound healing, but their application requires careful consideration of clinical context and patient-specific factors.Growth factors and cytokines play a crucial role in wound healing, with several being used clinically for non-healing wounds such as pressure ulcers, chronic venous ulcers, and diabetic foot ulcers. This review discusses four key growth factors and cytokines: granulocyte-macrophage colony stimulating factor (GM-CSF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF). While clinical results are encouraging, many studies have small sample sizes and varied endpoints, necessitating further research for definitive evidence of efficacy. GM-CSF, a cytokine present in wound beds, promotes wound healing by enhancing myofibroblast differentiation, inflammatory cell recruitment, and epidermal proliferation. It has been approved for use in certain clinical settings, with studies showing improved healing in chronic venous ulcers. However, its use is associated with minimal side effects. PDGF, involved in all stages of wound healing, has been shown to accelerate wound closure in diabetic foot ulcers. Becaplermin, a recombinant PDGF, has been approved for use in chronic venous ulcers but is associated with potential malignancy risks. bFGF promotes granulation tissue formation and re-epithelialization, with studies showing improved healing in pressure ulcers. VEGF is important for angiogenesis and has been used in treating diabetic wounds, though its efficacy in chronic venous ulcers is less established. Despite promising results, the use of these growth factors is limited by small study sizes, varied endpoints, and the need for larger randomized controlled trials. Additionally, the harsh environment of chronic wounds, characterized by protease activity and imbalanced collagenolytic activity, poses challenges for effective growth factor delivery. Debridement is essential to remove non-healing tissue and create a suitable microenvironment for growth factor activity. While exogenous growth factors show potential, their use should be combined with standard of care treatments and evaluated for safety and efficacy in future studies. The role of protease inhibitors in conjunction with debridement is also being explored to enhance growth factor activity in chronic wounds. Overall, growth factors and cytokines are essential for wound healing, but their application requires careful consideration of clinical context and patient-specific factors.