Melanoma is a heterogeneous disease for which monotherapies are likely to fail in the majority of patients due to genomic variations between individuals. Novel treatments, such as vemurafenib and ipilimumab, offer clinical promise in metastatic melanoma and the increased potential for combined therapeutic strategies, necessary given the differences in response between patients. Together with these new approaches, the development of clinically relevant biomarkers that predict treatment outcomes are required to ensure these new therapies are targeted at those patients most likely to benefit. Here we review the utility of some potential biomarkers of treatment response in patients with metastatic melanoma.