The innate immune system relies on a germ-line-encoded repertoire of pattern recognition receptors (PRRs), activated by deeply conserved pathogen signatures, such as bacterial cell wall components or foreign nucleic acids. To enable effective defence against invading pathogens and prevent from deleterious inflammation, PRR-driven immune responses are tightly controlled by a dense network of nuclear and cytoplasmic regulators. Long non-coding RNAs (lncRNAs) are increasingly recognized as important components of these regulatory circuitries, providing positive and negative control of PRR-induced innate immune responses. The present review provides an overview of the presently known roles of lncRNAs in human and murine innate antiviral and antibacterial immunity. The emerging roles in host defence and inflammation suggest that further mechanistic insights into the cellular functions of lncRNAs will decisively advance our molecular understanding of immune-associated diseases and open new avenues for therapeutic intervention.