Covering: up to November 2021Since its isolation in 1818, strychnine has attracted the attention of a plethora of chemists and pharmacologists who have established its structure, developed total syntheses, and examined its complex pharmacology. While numerous reviews on structure elucidation and total synthesis of strychnine are available, reports on structure-activity relationships (SARs) of this fascinating alkaloid are rare. In this review, we present and discuss structures, synthetic approaches, metabolic transformations, and the diverse pharmacological actions of strychnine and its mono- and dimeric analogues. Particular attention is given to its SARs at glycine receptors (GlyRs) in light of recently published high-resolution structures of strychnine-GlyR complexes. Other pharmacological actions of strychnine and its derivatives, such as their antagonistic properties at nicotinic acetylcholine receptors (nAChRs), allosteric modulation of muscarinic acetylcholine receptors as well as anti-cancer and anti-plasmodial effects are also critically reviewed, and possible future developments in the field are discussed.