The present review describes research on natural aziridine alkaloids isolated from both terrestrial and marine species, as well as their lipophilic semi-synthetic, and/or synthetic analogs. Over 130 biologically active aziridine-containing compounds demonstrate confirmed pharmacological activity including antitumor, antimicrobial, antibacterial effects. The structures, origin, and biological activities of aziridine alkaloids are reviewed. Consequently this review emphasizes the role of aziridine alkaloids as an important source of drug prototypes and leads for drug discovery.