In the past fifteen years, new “omics” technologies have created it doable to get high-resolution molecular snapshots of organisms, tissues, and even individual cells at numerous malady states and experimental conditions. it's hoped that these developments can commence a brand new era of customized medication within which a personality's molecular measurements area unit accustomed diagnose malady, guide medical care, and perform different tasks a lot of accurately and effectively than is feasible exploitation customary approaches. There currently exists a huge literature of rumored “molecular signatures”. However, despite some notable exceptions, several of those signatures have suffered from restricted reliableness in freelance datasets, lean sensitivity or specificity to satisfy clinical wants, or different challenges. During this paper, we tend to discuss the method of molecular signature discovery on the premise of omics knowledge. Specifically, we tend to highlight potential pitfalls within the discovery method, additionally as methods which will be accustomed increase the percentages of triple-crown discovery.