Soft tissue sarcomas, which originate from the mesenchymal tissue, represent a rare disease group with more than 100 subtypes. Primary treatment is surgical excision. In locally-advanced or metastatic cases, systemic treatment is the only therapeutic approach. Because of their heterogeneity, prognosis and response to the chemotherapy may be relatively different. Monotherapy with doxorubicin and its combination with ifosfamide continue to be the standard approach in the first-line treatment of advanced disease. Histology-directed therapy has become popular with the introduction of novel cytotoxic agents. Successful results have been achieved with recent developments in the field. Currently, the median overall survival rate in advanced stage disease barely exceeds 12 months in spite of the novel treatment options. In this review, our objective was to summarize the current data on cytotoxic treatments in the metastatic soft tissue sarcomas.