The author, as the third recipient of the E. E. Smissman Award, reflects on his career as a "classical" medicinal chemist. His research began with predoctoral work on improving morphine and codeine substitutes (central nervous system agents), followed by a 9-year hiatus during World War II focused on malaria (yielding phenanthrene alcohols) and tuberculosis (synthesizing amino- and guanidinophenyl glucosides/glucosaminides with no useful activity). Resuming analgesic research, he studied methadone derivatives (α/β-methadols, acetylated products) and later discovered 6,7-benzomorphans. A series of 2'-hydroxy-5 monoalkyl- and 5,9-dialkyl-α(β)-6,7-benzomorphans were synthesized, showing moderate to strong analgesic activity in mice (ED50 values) and low/no physical dependence in rhesus monkeys. N-substitution studies revealed phenethyl substitution on normetazocine produced phenazocine, a more potent analgesic with reduced abuse liability vs. morphine. The research relied on conventional structure-activity relationships, trial-and-error, and occasional intuition, with reflections on his "classical" approach compared to modern medicinal chemistry.