Following the completion of the Human Genome Project in 2003, sequencing has become one of the most influential tools in biomedical research. Sequencing took off in earnest with the development of next-generation sequencing techniques in the early 2000s, making sequencing high throughput, faster, more affordable and commercially available to individual laboratories. With the improved understanding of the role of genetics in human disease, coupled with rapid advancement in sequencing technology, we are progressively unlocking the secrets of how our genes control the development of diseases. This has the potential to revolutionize medicine and healthcare, providing a significant step towards personalized medicine. How did we arrive here? What are the major achievements of sequencing technologies of the past two decades and how does it help us to piece the clues together towards personalized treatments and diagnosis?