This Alfred Burger Award Lecture presents the results of recent investigations with colchicine and physostigmine. For colchicine, its therapeutic uses (acute gout attacks, Famililal Mediterranean Fever, chronic myelocytic leukemia, etc.), mechanism of action (inhibiting cellular mitosis by disrupting microtubule formation via tubulin polymerization inhibition), structural modifications (of methoxy groups in rings A and C, acetamido group in ring B, tropolonic ring C, and studies on atropisomerism) and their effects on antitubulin activity are discussed, along with exploration of allocolchicine compounds (ring-contracted analogues with retained tubulin polymerization inhibition activity) and potential markers for the colchicine binding site on tubulin. For physostigmine, its medical applications (glaucoma, organophosphate poisoning antidote, potential use in Alzheimer's disease), structural modifications (of carbamate side chain and N(1) methyl group), analgesic properties of eseroline and its analogues (e.g., HP-736), and efficient synthesis of optically active alkaloids (via resolution of racemic N(1)-noreseroline methyl ether using the phenylethyl urea method to prepare (+)-physostigmine and congeners) are covered, including evaluations of cholinesterase inhibition activity of modified analogues.