Long non-coding RNA (lncRNA) was once considered to be the "noise" of genome transcription without biological function. However, increasing evidence shows that lncRNA is dynamically expressed in developmental stage or disease status, playing a regulatory role in the process of gene expression and translation. In recent years, lncRNA is considered to be a core node of functional regulatory networks that controls cardiac and also involves in multiple process of heart failure such as myocardial hypertrophy, fibrosis, angiogenesis, etc., which would be a therapeutic target for diseases. In fact, it is the development of technology that has improved our understanding of lncRNAs and broadened our perspective on heart failure. From transcriptional "noise" to star molecule, progress of lncRNAs can't be achieved without the combination of multidisciplinary technologies, especially the emergence of high-throughput approach. Thus, here, we review the strategies and technologies available for the exploration lncRNAs and try to yield insights into the prospect of lncRNAs in clinical diagnosis and treatment in heart failure.