Genomic rearrangements of the locus 11q23 are frequently observed in aggressive acute leukemias with poor prognosis. These chromosomal aberrations fuse the mixed-lineage leukemia (MLL) gene to one of more than 50 partners. The resulting mixed-lineage leukemia fusions often code for chimeric transcriptional activators, which are able to transform normal hematopoietic cells through the deregulation of leukemogenic target genes. This review provides a concise overview about the known functions encoded in MLL and the respective fusion partners. Additionally, the roles of some target genes, as well as co-factors of mixed-lineage leukemia fusion proteins, are described with an emphasis on recent advances potentially uncovering novel therapeutic targets.