Paolo Ascierto, MD of the National Tumor Institute Fondazione G. Pascale, Naples, Italy discusses drug combinations in melanoma as part of his overview of his talk on the best use of immunotherapy in melanoma held at the World Congress on Cancers of the Skin (WCCS) and the Congress of the European Association of Dermato-Oncology (EADO) in Vienna, Austria. Prof. Ascierto talks about combining immunotherapy with all the other tools that are available for the treatment of advanced melanoma, including chemotherapy and targeted therapy. In the future, some other combinations of therapy will be seen. Further, how to sequence or combine treatment will be an issue in future. There are several trials, such as the SECOMBIT trial (NCT02631447), a randomized Phase III trial looking at the combination of target agents (LGX818 plus MEK162) and the combination of immunomodulatory antibodies (ipilimumab plus nivolumab) in patients with metastatic melanoma and BRAF V600 mutation. There is an interesting third arm to the trial called sandwich – to start with targeted therapy for eight weeks followed by combination immunotherapy (nivolumab combined with ipilimumab) until progressive disease (PD); then targeted therapy until PD. There is a parallel biomarker study, which is important to understand the mechanism to resistance.