An editorial questions whether this new combination of encorafenib–binimetinib is too late an addition to the resources clinicians have against BRAF-mutated metastatic melanoma. It notes that this combination is being investigated at a time when immunotherapy is progressively taking the leading role in the therapeutic strategy, when vemurafenib–cobimetinib and dabrafenib–trametinib are already being tested in triplet with immunotherapy, and when dabrafenib–trametinib has already proved to be active in the adjuvant treatment of high-risk stage III BRAF-mutant melanoma. It suggests that despite this late development, clinicians should keep in mind that survival of many patients with metastatic melanoma is still dependent on a long-term treatment with BRAF–MEK inhibitor combinations. It adds that if confirmed, “the attractive tolerability profile of encorafenib–binimetinib would be an advantage in first-line prescription, for re-introduction after immunotherapy failure, for patients with a persistent poor tolerance for BRAF-MEK inhibitor combinations who might benefit from a switch to encorafenib–binimetinib, in facilitating combinations with immunotherapy in triplets, and for extending the scope of adjuvant treatment to less advanced melanoma.”