Acute myeloid leukemia (AML) is categorized by an increase in the number of myeloid cells in the marrow and an arrest in their maturation, frequently resulting in hematopoietic insufficiency. A common theme in acute myeloid leukaemia (AML) associated with balanced reciprocal translocations is the involvement of transcription factors as one or both of the fusion partners. Transcription factors commonly involved in chromosomal translocations include core binding factor (CBF), retinoic acid receptor alpha (RARα), mutations of the NPM1, FLT3, and CEBPA genes. The panel of known molecular markers is continuously increasing, for example, considering the recently described TET2 and IDH1 mutations. Monitoring of the minimal residual disease load with quantitative real-time PCR can be performed for NPM1 and other mutation cases. In addition, the recruitment of transcriptional co-activators and co-repressors by these transcription factors suggests that these proteins also may play a critical role in leukaemogenesis. CBP and p300 have been recently cloned. Treatment for patients younger than 60 years consists of cytotoxic “chemotherapy” and might cure 20–75%, depending primarily on leukemia cell cytogenetics. However, chemotherapy produces such a result in less than 10% of elderly patients because of their inability to survive treatment and, mainly, the association of old age with cytogenetic abnormalities involving chromosomes 5 and 7.The introduction of next generation sequencing will certainly catalyze the molecular characterization of AML.