The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor and evolutionary member of the immunoglobulin superfamily that is involved in the host response to infection, injury, and inflammation. It exists in two forms: membrane-bound and soluble forms (sRAGE). RAGE recognizes a variety of ligands and, via a receptor-driven signaling cascade, activates the transcription factor NF-κB, leading to the expression of proinflammatory cytokines. The soluble form, sRAGE, is a decoy receptor and competitively inhibits membrane RAGE activation. RAGE is constitutively expressed abundantly in the lung under basal conditions. This expression is enhanced during inflammatory states such as with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This review summarizes the characteristics of RAGE, RAGE isoforms, RAGE ligands, and signaling pathways in the pathogenesis of ALI and ARDS. Additionally, the review explores the potential of RAGE as an important therapeutic target in ALI/ARDS.