Respiratory infections caused by viral pathogens, including influenza A virus, respiratory syncytial virus, and SARS-CoV-2, as well as bacterial pathogens, remain major contributors to global morbidity and mortality. The outcomes of these infections are largely determined by how the host innate immune system detects pathogen-derived nucleic acids and regulates subsequent inflammatory responses. Pattern recognition receptors (PRRs) located in endosomal and cytosolic compartments, including Toll-like receptors, RIG-I-like receptors, absent in melanoma 2, and Z-DNA-binding protein 1, as well as the cyclic GMP-AMP synthase-stimulator of interferon genes pathway, recognize viral and bacterial nucleic acids and initiate signaling cascades that promote cytokine production and antimicrobial defense. However, dysregulated PRR activation can trigger inflammatory programmed cell death, including apoptosis, pyroptosis, necroptosis, and PANoptosis. This review summarizes recent advances in understanding how nucleic acid sensing orchestrates inflammatory cell death during respiratory infections, with particular emphasis on pathogen- and cell type-specific mechanisms that shape disease outcomes. We further highlight the dual nature of these pathways, which are essential for pathogen clearance but can drive immunopathology when excessively activated. Defining how nucleic acid-sensing pathways shape inflammatory cell death in respiratory infections may guide host-directed therapies that enhance pathogen clearance while preserving lung function. Overall, the field remains constrained by the predominance of virus-focused and murine preclinical studies, whereas bacterial nucleic acid sensing during respiratory infections remains poorly defined. Future studies should integrate major bacterial infection models with human-relevant respiratory epithelial systems to better translate PRR-mediated immune mechanisms into host-directed therapeutic strategies.