<p>Long non-coding RNAs (lncRNAs) are a diverse group of regulatory molecules exceeding 200 nucleotides in length. They modulate gene expression through multiple mechanisms, including transcriptional, post-transcriptional, and translational processes. LncRNAs play crucial roles in both normal and pathological biological processes. Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. This highlights the need for a more systematic understanding of the underlying molecular mechanisms to inform the development of novel therapeutic interventions. Substantial evidence indicates that lncRNAs play a vital role in regulating fundamental processes during cardiac development and homeostasis. The disruption of lncRNA expression patterns significantly contributes to CVD development. Specific lncRNAs modulate several key factors in atherosclerosis, including endothelial dysfunction, lipid metabolism, and inflammatory responses within arterial walls. During myocardial infarction, distinct molecular signatures influence cardiomyocyte survival, inflammatory cascades, and tissue remodeling. Pathological cardiac hypertrophy involves dysregulation of lncRNAs that control sarcomeric organization, calcium handling, and fibrotic responses. These molecules regulate metabolic reprogramming, contractile dysfunction, and maladaptive remodeling during the progression of heart failure. Because of their tissue-specific expression patterns and presence in circulating biofluids, lncRNAs also have significant potential as biomarkers for disease diagnosis and prognosis. Furthermore, their regulatory functions position them as attractive therapeutic targets, with emerging strategies, including antisense oligonucleotides and small-molecule modulators, showing promise in preclinical studies. This review integrates mechanistic insights with emerging translational data to demonstrate how lncRNAs could enhance current diagnostic and therapeutic approaches for CVD.</p> Graphical Abstract <p></p>