The potential of 4-thiazolidones (2,4-thiazolidinediones, 2-thioxo(imino)-4-thiazolidones) as drugs is under consideration by the pharmaceutical science since the beginning of the XX century. During recent years a new phase has been seen in this field. Centerarian history of synthetic research possibilities of these heterocycles lead to diversity in modelling biologically active compounds using 4-thiazolidone scaffolds. Modification of the 4- thiazolidone cycle on 2-, 3-, 4- or 5-position is successful to achieve synthetic products with a wide spectrum of pharmacological activity and has received considerable attention in this review. Currently 4-thiazolidones are considered as a new class of antidiabetic (insulin-sensitising) drugs and potent aldose reductase inhibitors, which possess potential for the treatment of diabetes complications (cataract, nephropathy, neuropathy). Novel 4- thiazolidones are undergoing different stages of clinical trials as potential thyromimetic, antimicrobial, antiviral, anti-ischaermic, cardiovascular, anticancer drugs.