We note with sadness the death of Hugh de Wardener on September 29, 2013 at the age of 98. He was truly a pioneer and early developer of the specialty of Nephrology whose seminal contributions have been well described recently by Schrier.1 To us, he was a creative and inspirational innovator in the field to which we devoted most of our investigative effort during our career—the search for a natriuretic hormone. As our final tribute to him, we would like to recognize his seminal contributions to that field and offer our brief assessment of the long-term importance of those contributions. In a 1957 review of the literature, Smith2 postulated the existence of a humoral substance that controlled renal sodium excretion. Smith speculated that this sodium-regulating hormone was analogous to the free-water–regulating antidiuretic hormone, and hence it was an antinatriuretic hormone. Four years later, in 1961, de Wardener et al3 demonstrated a transferrable natriuretic factor in cross-circulated blood from volume-expanded dogs to euvolemic dogs and proposed the existence of a natriuretic hormone. This provocative article led to an explosion of investigative activity and established de Wardener as …