Sarcomas are relatively uncommon and heterogeneous malignancies in terms of clinical presentation, histology, genetic and molecular profiles and aggressiveness. To date, the only effective management for most sarcomas is surgical resection with adequate margins. The role of adjuvant therapies is quite limited and depends on the status of surgical margins, tumor histologic type and grade. Unfortunately, a considerable number of patients may suffer from tumor metastases which are often refractory to current treatment strategies and constitute the primary cause of sarcoma-related death. Accordingly, it is very important to pay attention not only to elucidate the molecular determinants correlated with tumor invasion and metastatic spread but also to understand evolution of potential therapeutics, especially targeted therapies. Recent advances in this field include the identification of specific chromosomal translocations and genetic amplifications, characterization of some important signaling pathways such as mTOR or insulin-like growth factor pathway, and also the development in angiogenesis knowledge. More importantly, brand new agents like viruses and the targeting of tumor-specific metabolism have led to the development of new therapeutic options with promising results.