One late afternoon in the beginning of January 1986, bicycling from the lab over the hill to the small village of Fullbourn, the idea for an alternative DNA sequencing technique came to my mind. The basic concept was to follow the activity of DNA polymerase during nucleotide incorporation into a DNA strand by analyzing the pyrophosphate released during the process. Today, the technique is used in multidisciplinary fields in academic, clinical, and industrial settings all over the word. The technique can be used for both single-base sequencing and whole-genome sequencing, depending on the format used. In this chapter I will give my personal account of the development of Pyrosequencing--beginning on a winter day in 1986, when I first envisioned the method--until today, nearly 20 yr later. I will conclude with future prospects for the method.