Wiesner made remarkable contributions to the structural and synthetic chemistry of complex polysubstituted polycyclic natural products. In the 1950s, prior to the development of nuclear magnetic resonance spectroscopy, he determined the structure of several diterpene alkaloids including veatchine, atisine, annotinine, delphinine, aconitine, and songorine. After returning to New Brunswick from Ayerst in 1964, he began a successful program to synthesize these compounds, culminating in the total synthesis of chasmanine and napelline. Towards the end of the 1970s Wiesner turned his attention to digitalis derivatives, with the goal of finding cardiac glycosides with safer therapeutic ratios. In the last decade of his career he succeeded in demonstrating the separation of the inotropic and toxic properties of this group of compounds, elucidated the underlying chemical mechanism, and finally achieved the total synthesis of digitoxin and other cardioactive steroids.