A review article described the chemistry of 4-thiazolidinones particularly rhodanine ring and different approaches for its reactions which included the modification of the ring. Besides, the reactivity of rhodanine ring which helped in the synthesis of different arylidenes at position 5 and carboxylic acids at position 3 The most reactive positions in 4-thiazolidinone are 3 and 5, which determine the major directions of heterocycle modification. Approaches to the synthesis of 3,5-disubstituted 4-thiazolidinones in general include two pathways. The first one was throughout the synthesis of 3,5-disubstituted 4-thiazolidinones by different reactions in position 3 of the thiazolidinone cycle. The second was the synthesis of 3,5-disubstituted 4-thiazolidinones by diverse reactions in position 5 of the thiazolidinone cycle Modification of 4-thiazolidinone cycle on positions 2, 3, 4 or 5 was successful to achieve synthetic products with a wide spectrum of pharmacological activity Currently 4-thiazolidinones were considered as a new class of antidiabetic (insulinsensitizing) drugs and potent aldose reductase inhibitors, which possess the potential for the treatment of diabetes complications (cataract, nephropathy, neuropathy).