Rhodanines, thiazolidine-2,4-diones and pseudothiohydantoins have become a very interesting class of heterocyclic compounds since the introduction of various glitazones and epalrestat into clinical use for the treatment of type II diabetes mellitus and diabetic complications, respectively. Chemical modifications of these heterocycles constantly result in compounds with a wide spectrum of pharmacological activities. 5-Arylidenerhodanines are frequently identified as potent hits in high throughput screening against various prokaryotic and eukaryotic targets. Synthesis of substituted rhodanines, based on high throughput screening hits, often leads to potent and selective modulators of targeted enzymes or receptors, which exert their pharmacological activities through different mechanisms of action. Due to various possibilities of chemical derivatization of the rhodanine ring, rhodanine-based compounds will probably remain a privileged scaffold in drug discovery. We have therefore reviewed their biological activities, mechanism of action, structure activity relationship and selectivity against other targets.