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Since the very first medical use of dexamethasone (DEX) in 1958, this glucocorticoid (GC) has been widely used in various clinical applications. Compared to other GCs, DEX is highly potent and comes in multiple formulations for ease of local and systemic administrations. Recently, DEX has a new application for treating COVID-19 patients. DEX mainly inhibits expressions of inflammatory proteins and transcription factors necessarily for cell proliferation. DEX can both upregulate and downregulate expressions of the genes that facilitates anti- inflammatory effects and immunosuppression. Key proteins involved in DEX pathways are NF- B, AP-1, COX-2, and annexin A1. When used appropriately, DEX can minimize inflammatory pain and damage but it can also delay patient recovery by immunosuppression. Due to this duality, DEX should be used with caution for treatment considerations. Long-term systemic use could lead to debilitating adverse reactions and firm recommendations should be established in treating both acute and chronic disease with DEX.