The EWS-FLI1 fusion resulting from the specific t(11;22)(q24;q12) of Ewing's sarcoma was the first sarcoma gene fusion to be cloned, a decade ago. Moving from the cloning of this oncogenic chimeric transcription factor to the further elucidation of its pathogenetic mechanisms has revealed new complexities in the biology of this tumor which may be relevant to other fusion oncogenes as well. The present review highlights recent advances in three avenues of investigation that are providing new insights into this particular neoplasm and into the biology of EWS-FLI1 and related fusion proteins, namely the identification of various mitogenic targets of this aberrant transcription factor, its possible role as a deregulator of splicing, and the role of the p53 pathway in modulating its oncogenicity.