Trained immunity is a long-term, non-specific memory-like response in innate immune cells, enabling them to respond more robustly to subsequent infections. This phenomenon is mediated by metabolic rewiring and epigenetic modifications, allowing innate immune cells to retain enhanced responsiveness even after initial exposure to pathogens or sterile inflammation. Unlike adaptive immunity, which relies on antigen-specific memory, trained immunity is characterized by a generalized enhancement of innate immune protection, enabling a quicker and more efficient defense against a broad range of pathogens. Trained immunity has been observed in various innate immune cell populations, including monocytes, macrophages, dendritic cells, natural killer (NK) cells, and innate lymphoid cells (ILCs). It is also present in non-immune cells such as epithelial stem cells and fibroblasts, contributing to tissue repair and regeneration. The induction of trained immunity is influenced by various stimuli, including microbial products like β-glucan and sterile inflammation, which trigger epigenetic changes and metabolic reprogramming. These changes lead to the activation of pro-inflammatory genes and enhanced cytokine production, resulting in improved immune responses. Trained immunity has been shown to confer protection against infections such as tuberculosis, malaria, and candidiasis, and is associated with reduced mortality and improved outcomes in vaccinated individuals. However, its overactivation can contribute to the pathogenesis of autoinflammatory and autoimmune disorders. Understanding the mechanisms underlying trained immunity is crucial for developing therapeutic strategies to enhance immune responses and treat immune-related diseases.Trained immunity is a long-term, non-specific memory-like response in innate immune cells, enabling them to respond more robustly to subsequent infections. This phenomenon is mediated by metabolic rewiring and epigenetic modifications, allowing innate immune cells to retain enhanced responsiveness even after initial exposure to pathogens or sterile inflammation. Unlike adaptive immunity, which relies on antigen-specific memory, trained immunity is characterized by a generalized enhancement of innate immune protection, enabling a quicker and more efficient defense against a broad range of pathogens. Trained immunity has been observed in various innate immune cell populations, including monocytes, macrophages, dendritic cells, natural killer (NK) cells, and innate lymphoid cells (ILCs). It is also present in non-immune cells such as epithelial stem cells and fibroblasts, contributing to tissue repair and regeneration. The induction of trained immunity is influenced by various stimuli, including microbial products like β-glucan and sterile inflammation, which trigger epigenetic changes and metabolic reprogramming. These changes lead to the activation of pro-inflammatory genes and enhanced cytokine production, resulting in improved immune responses. Trained immunity has been shown to confer protection against infections such as tuberculosis, malaria, and candidiasis, and is associated with reduced mortality and improved outcomes in vaccinated individuals. However, its overactivation can contribute to the pathogenesis of autoinflammatory and autoimmune disorders. Understanding the mechanisms underlying trained immunity is crucial for developing therapeutic strategies to enhance immune responses and treat immune-related diseases.