The focus of this paper is to cover the evolution in the pharmacologic approach in the treatment of sarcoma. As early as conservative treatment all the way through recent advances and other promising treatments which are under investigation. Nowadays, no universal approach had been adopted in the treatment of sarcoma creating an urge to investigate potential agents improving the overall prognosis of the chaotic malignancy. Surgery and radiotherapy remain an integral part of therapy and are routinely used in the treatment of sarcomas, the pharmacologic approach is based on chemotherapy with an emphasis of agents such as cytotoxins, targeted epigenetic, immune therapy, checkpoints inhibitors, adoptive immunity.