Single-molecule enzymology has a longer history than is often supposed, with the first measurements being made as early as 1961. However, the development of new technologies has meant that most of the progress has been made in the last two decades. I review the development of single-molecule enzymology, focussing on five key papers which are milestones in the field. In particular, I discuss the 1961 paper by Boris Rotman, which made inventive use of what now seems like primitive technology, and continues to be influential to this day.
