Extremity soft-tissue sarcomas are a heterogeneous group of rare neoplasms, characterized by a broad spectrum of biological aggressiveness and a uniform tendency for local failure if not adequately treated. Surgery is the mainstay of therapy, and the availability of multidisciplinary surgical skills allows adequate margins with acceptable morbidity to be obtained. Local therapies, such as radiation therapy or isolated limb perfusion, alone or in combination with systemic agents, may help to further improve local control, especially in difficult presentations. The possible impact of systemic treatment on survival is still a matter of debate, and the agents used so far have not provided a major breakthrough, even in selected populations at high risk of disease spread. Nevertheless, soft-tissue sarcomas are no longer considered a unique disease. More than 50 different histotypes can now be well recognized, with distinct biological and molecular characteristics, which lead to different clinical behavior and a potentially different sensitivity to targeted agents. Therefore, it is more essential than ever for treatment of these patients to be delivered in referral centers, where a dedicated multidisciplinary team is able to administer histology and clinically driven approaches. The employment of combined modalities will be able to maximize the chance of local cure even in difficult presentations, and possibly improve survival, especially in high-risk disease.