The article reviews the critical transition from inflammation to proliferation during wound healing, emphasizing its significance in both normal and impaired healing processes. The transition is a key step that, when compromised, can lead to chronic wounds and excessive scarring. The review highlights the roles of various cellular and molecular factors, including macrophages, fibroblasts, bioactive lipid mediators, reactive oxygen species (ROS), toll-like receptors (TLRs), transcription factors, and microRNAs. Macrophages, for instance, play a crucial role in resolving inflammation and promoting proliferation by switching from a pro-inflammatory M1 phenotype to a reparative M2 phenotype. Fibroblasts, through their production of growth factors and matrix components, are essential for forming granulation tissue and restoring skin structure. Bioactive lipid mediators, such as eicosanoids and endocannabinoids, regulate both inflammation and proliferation. ROS, while normally protective, can become detrimental in excessive amounts, leading to oxidative stress. TLRs, which initiate the inflammatory response, have inhibitory mechanisms that limit their signaling to facilitate the transition to the proliferative phase. Transcription factors like glucocorticoid receptors, androgen and estrogen receptors, peroxisome proliferator-activated receptors (PPARs), activator protein 1 (AP-1), E2F transcription factors, Smad proteins, early growth response 1 (EGR1), and homeobox genes also regulate the inflammatory and proliferative phases. Epigenetic mechanisms, including DNA methylation and histone modifications, further modulate gene expression during wound healing. Understanding these mechanisms is crucial for developing more effective therapeutic interventions for chronic wounds and improving wound healing outcomes.The article reviews the critical transition from inflammation to proliferation during wound healing, emphasizing its significance in both normal and impaired healing processes. The transition is a key step that, when compromised, can lead to chronic wounds and excessive scarring. The review highlights the roles of various cellular and molecular factors, including macrophages, fibroblasts, bioactive lipid mediators, reactive oxygen species (ROS), toll-like receptors (TLRs), transcription factors, and microRNAs. Macrophages, for instance, play a crucial role in resolving inflammation and promoting proliferation by switching from a pro-inflammatory M1 phenotype to a reparative M2 phenotype. Fibroblasts, through their production of growth factors and matrix components, are essential for forming granulation tissue and restoring skin structure. Bioactive lipid mediators, such as eicosanoids and endocannabinoids, regulate both inflammation and proliferation. ROS, while normally protective, can become detrimental in excessive amounts, leading to oxidative stress. TLRs, which initiate the inflammatory response, have inhibitory mechanisms that limit their signaling to facilitate the transition to the proliferative phase. Transcription factors like glucocorticoid receptors, androgen and estrogen receptors, peroxisome proliferator-activated receptors (PPARs), activator protein 1 (AP-1), E2F transcription factors, Smad proteins, early growth response 1 (EGR1), and homeobox genes also regulate the inflammatory and proliferative phases. Epigenetic mechanisms, including DNA methylation and histone modifications, further modulate gene expression during wound healing. Understanding these mechanisms is crucial for developing more effective therapeutic interventions for chronic wounds and improving wound healing outcomes.