Studies done in the past on the 4-thiazolidinone nucleus have shown that derivatives containing this nucleus have a significant potential to be developed as powerful medicinal agents. Due to these biological actions, medicinal chemists have developed an interest in the structure-activity relationship of these compounds, which has resulted in the discovery of several lead molecules. For the benefit of medicinal chemists working on this nucleus, this review outlines the routes for its synthesis and covers older and more recent studies on its biological activity. The review discusses current findings about thiazolidin-4-ones' anti-inflammatory, analgesic, anticonvulsant, antidiabetic, antiparasitic, antibacterial, antitubercular, antioxidant, and anticancer activities.