Anaplastic astrocytomas (WHO grade III) constitute about 10% of all gliomas. Definitive data on predictive and prognostic factors are lacking for these neoplasms that are considered the most enigmatic entity among the whole spectrum of astrocytic tumors because of their unclear biologic behavior and variable clinical outcome. Currently, only few factors have been identified as useful for prognosis of anaplastic astrocytoma: age and Karnofsky Performance Status. Attempts have been made to identify biological prognostic factors for response to therapy and clinical outcome, as well as potential targets for new therapies. Potential prognostic biomarkers concern tumor suppressor genes on chromosome 9q that are involved in the RB1 pathway; PTEN, the PI3k/Akt/p70s6k cascade, survivin gene, Formylpeptide receptor, minichromosome maintenance protein 3 and genes on chromosome 7. Furthermore, some angiogenic factors (e.g. hypoxia-inducible factor-1α, vascular endothelial growth factor and scatter factor/hepatocyte growth factor) and the methylation status of O6-methylguanine-DNA methyltransferase gene (one of the main effectors of DNA repair system) are emerging novel putative determinants of prognosis. Moreover, recent studies on magnetic resonance imaging characteristics give prognostic significance to the presence of necrosis and enhancement. The state of the art pictured here underlie the recent interest on gene expression profile to identify aberrations useful to understand the biologic behavior of astrocytic tumors. Our knowledge in this field is still limited, and remains an issue of great concern.