Heart failure (HF) is a widespread cardiovascular condition that poses significant risks to a wide spectrum of age groups and leads to terminal illness. Although our understanding of the underlying mechanisms of HF has improved, the available treatments still remain inadequate. Recently, long non-coding RNAs (lncRNAs) have emerged as crucial players in cardiac function, showing possibilities as potential targets for HF therapy. These versatile molecules interact with chromatin, proteins, RNA, and DNA, influencing gene regulation. Notable lncRNAs like Fendrr, Trpm3, and Scarb2 have demonstrated therapeutic potential in HF cases.