Evaluation of: Bejar R, Lord A, Stevenson K, et al. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood 2014 Oct 23;124(17):2705-12. Patients with myelodysplastic syndromes (MDS) have clinically variable courses even within the same prognostic subgroups. Although hypomethylating agents (HMAs) have been shown to improve outcomes in patients with high-risk MDS, many patients do not derive benefit. There is an urgent clinical need to identify patients with low probability of benefiting from HMAs but no reliable clinical predictors or biomarkers have been discovered to date. Although some recurrent molecular mutations in MDS carry independent prognostic value, their ability to predict benefit from HMAs is not clear. Here, we discuss an important article in which sequencing from samples of 213 patients identified recurrent mutations associated with response to HMAs. Although an important step in the right direction, the clinical implications of these findings are far from optimal and identification of biomarkers that can reliably predict benefit from HMAs and other therapies in patients with MDS remains a top clinical and a research priority.