This chapter is a scientific autobiography summarizing my research from its beginnings as a medical student to heading a research group. I started as an immunologist but the themes of my research led me to unexpected directions and methodologies, combining biochemistry, cell biology, and molecular biology. My first wish was to devise an in vitro model of the effector arm of cell-mediated immunity. This took me to lymphokines and to macrophage activation by lymphokines. Since macrophage activation was associated with enhanced production of reactive oxygen species (ROS), I decided to first learn about the enzyme generating the primary ROS, superoxide. The design of a cell-free system, in which the superoxide-forming NADPH oxidase of resting phagocytes was activated by arachidonic acid and other anionic amphiphiles, was the turning point in my career, establishing in vitro reductionism as the dominant approach in my research. In 46 sections I describe my contribution, over a period of five decades, to deciphering the mechanism of activation of the catalytic component of the NADPH oxidase, Nox2, by the cytosolic components. The chapter also stresses the importance of interplay between personality and the familial, historical, educational, social, and ethical environments in shaping the achievements of a scientist.