Sarcomas are a rare and heterogeneous group of mesenchymal malignancies that have historically been challenging in diagnosis and treatment. In soft tissue sarcomas (STS), the recognition of different histological subtypes has made a dramatic conceptual change leading to histotype-driven targeted therapies. In gastrointestinal stromal tumors (GIST), the most important advance in the past decade was the demonstration that tyrosine kinase inhibitors (TKIs) can durably control disease and lead to remarkable treatment responses. The advent of TKIs has unquestionably changed the overall survival of patients with GIST, not only in the advanced-disease setting but also in individuals with high-risk disease. This review covers the latest clinical study highlights for STS and GIST presented at American Society of Clinical Oncology (ASCO) 2015 meeting, demonstrating the constant progress from conventional chemotherapy to histology-driven therapy approaches.