Soft tissue sarcomas are rare cancers but because of their association with characteristic chromosomal translocations and activating mutations they may be particularly susceptible to molecularly targeted therapies. Gastrointestinal stromal tumour (GIST) became the paradigm for targeted therapy in solid tumours owing to the success of imatinib, which has transformed the prognosis in this disease. Translocation-driven tumours have proved harder to target, but the impact of fusion proteins on gene expression is beginning to be understood and may also reveal new targets for therapy, such as insulin-like growth factor 1 receptor, now that effective inhibitors have been discovered. Angiogenesis inhibition also appears to be a promising area for research in sarcomas and many new targets are emerging at the same time as agents capable of investigating them in the clinic are being developed. It is not unrealistic to hope that targeted therapies will play an increasing role in the management of sarcomas in the near future.