150 years ago, in October 1869, Friedrich Miescher completed his work on one of the great scientific discoveries of our time; the isolation and identification of DNA, “Nuclein”, as a central cellular component. However, just how important DNA is in the biology of the cell would not be demonstrated for another 75 years, when in 1944 Avery, MacLeod and McCarthy showed that it is the molecule of inheritance. From here, DNA rapidly went on to capture the scientific and public imagination and over the next 75 years became integral to our understanding of life. Yet the man who first discovered it still lingers in relative obscurity, often not even remembered by scientists who work closely with nucleic acids. On this sesquicentennial anniversary, we look back to just how this monumental discovery was accomplished, who the man behind it was, and how he tried to understand Nuclein’s role in the cell in the context of his day. Perhaps now is the right time for Miescher’s legacy to return to the spotlight.