Diffuse gliomas are the most common primary malignant brain tumors in adults and continue to be almost universally fatal. Nevertheless, a striking variability in outcome has long been observed, with a subset of patients having prolonged survival. Recent molecular discoveries have provided new insights into gliomagenesis and have enhanced clinical subclassification of gliomas. Mutations in the isocitrate dehydrogenase (IDH) genes occur frequently in low-grade astrocytomas and oligodendrogliomas (World Health Organization [WHO] grade II), and in higher-grade gliomas (WHO grades III and IV) that arise after malignant progression of low-grade tumors. IDH mutation has an established role as a favorable prognostic marker; however, the utility of IDH mutation in guiding treatment is still under investigation. A subset of IDH-mutant tumors, predominantly oligodendrogliomas, also harbor codeletion of chromosomes 1 p and 19q, a feature that predicts responsiveness to chemotherapy. Here, we review the current data regarding the prognostic and predictive value of IDH mutation and 1 p/19q codeletion in gliomas. We also discuss possible management algorithms using these biomarkers to tailor surgical and adjuvant therapy for specific diffuse gliomas. Ultimately, understanding the natural history of glioma subtypes and the predictive value of genetic markers may maximize survival and minimize treatment morbidity.