Folate serves as a cofactor for one-carbon (1C) transfer reactions. These reactions are involved in the synthesis of DNA nucleotides, the amino acid methionine, and in the regulation of homocysteine (Hcy) levels. Emerging evidence suggests that these reactions have roles in the development and maintenance of inflammatory responses, with optimal folate availability having key importance in preventing endothelial dysfunction and DNA instability. Low folate levels are commonly observed in chronic inflammatory diseases, indicating that inadequate folate may be involved in the pathogenesis of inflammatory conditions or that chronic inflammation increases folate requirements. These findings highlight folate interventions as a potential treatment in inflammatory disorders. However, current understanding of folate and its influence on inflammatory phenotypes is limited. Evidence indicates that the relationship between folate and inflammation is dependent on several factors, including the timing of intervention, dosage, and interaction with environment and genes. These factors require further investigation before recommendations for folate intake can be made for the prevention and treatment of inflammation. This review outlines the emerging role of folate in inflammation and key factors that may influence this relationship.