The recent discovery that thousands of RNAs are transcribed by the cell but are never translated into protein, highlights a significant void in our current understanding of how transcriptional networks regulate cellular function. This is particularly astounding when we consider that over 75% of the human genome is transcribed into RNA, but only approximately 2% of RNA is translated into known proteins. This raises the question as to what function the other so-called ‘non-coding RNAs’ (ncRNAs) are performing in the cell. Over the last decade, an enormous amount of research has identified several classes of ncRNAs, predominantly short ncRNAs (<200 nt) that have been confirmed to have functional significance. Recent advances in sequencing technology and bioinformatics have also allowed for the identification of a novel class of ncRNAs, termed long ncRNA (lncRNA) (>200 nt). Several studies have recently shown that long non-coding RNAs (lncRNAs) are associated with tissue development and disease, particularly in cell types that undergo differentiation such as stem cells, cancer cells and striated muscle (skeletal/cardiac). Therefore, understanding the function of these lncRNAs and designing strategies to detect and manipulate them, may present novel therapeutic and diagnostic opportunities. This review will explore the current literature on lncRNAs in skeletal and cardiac muscle and discuss their recent implication in development and disease. Lastly, we will also explore the possibility of using lncRNAs as therapeutic and diagnostic tools and discuss the opportunities and potential shortcomings to these applications.