I shall briefly describe how the ubiquitin system was discovered and then will discuss what general lessons can be learned from this story. One is the importance of having excellent mentors at an early stage of the scientific career, whose influence may greatly affect much of subsequent work. Another is choosing a research subject that is important, but not yet in the mainstream of scientific research. The importance of recognizing accidental observations that lead to novel discoveries and of staying away from “fashionable” technologies (unless absolutely necessary) will also be discussed.