Fat infiltration in skeletal muscle (myosteatosis) is a distinct disease from sarcopenia, directly linked to declining muscle capacity. This review summarizes the triggers and regulatory mechanisms of fat infiltration in skeletal muscle. Key triggers include aging, metabolic diseases, non-metabolic diseases, and muscle injury. Cellular origins of fat infiltration involve myogenic and non-myogenic cells, such as myogenic cells, fibro/adipogenic progenitors (FAPs), and endothelial cells. Molecular mechanisms involve signaling pathways like cAMP-PKA, hedgehog, Wnt/β-catenin, MAPK, miRNAs, and lncRNAs, which regulate lipid metabolism and adipogenesis. Detection methods include imaging techniques like CT, MRI, and QUS. Intervention strategies include exercise, diet, secreted factors, and gut microbiota. Nutritional interventions such as vitamin D, vitamin A, retinoic acid, conjugated linoleic acid (CLA), and linseed show potential in regulating fat infiltration. Plant extracts and myokines also play roles in modulating fat infiltration. Understanding these mechanisms is crucial for maintaining skeletal muscle health and treating muscle-related diseases.Fat infiltration in skeletal muscle (myosteatosis) is a distinct disease from sarcopenia, directly linked to declining muscle capacity. This review summarizes the triggers and regulatory mechanisms of fat infiltration in skeletal muscle. Key triggers include aging, metabolic diseases, non-metabolic diseases, and muscle injury. Cellular origins of fat infiltration involve myogenic and non-myogenic cells, such as myogenic cells, fibro/adipogenic progenitors (FAPs), and endothelial cells. Molecular mechanisms involve signaling pathways like cAMP-PKA, hedgehog, Wnt/β-catenin, MAPK, miRNAs, and lncRNAs, which regulate lipid metabolism and adipogenesis. Detection methods include imaging techniques like CT, MRI, and QUS. Intervention strategies include exercise, diet, secreted factors, and gut microbiota. Nutritional interventions such as vitamin D, vitamin A, retinoic acid, conjugated linoleic acid (CLA), and linseed show potential in regulating fat infiltration. Plant extracts and myokines also play roles in modulating fat infiltration. Understanding these mechanisms is crucial for maintaining skeletal muscle health and treating muscle-related diseases.