Sharing the Milstein Award with George R. Stark and Ian M. Kerr in the fall of 1997 brought this invitation to record personal reflections on our experiments concerning the mechanisms of action of interferon. Our work and that of the Kerr and Stark laboratories uncovered the Jak-Stat pathway through which signals from cell surface receptors reach genes in the cell nucleus. This review concentrates on that to which I can speak most reliably, that is, experiments done by my young colleagues at Rockefeller University.