Summary: Melanoma is a malignant neoplasm with the highest mortality rate among skin cancers. Mutations in the BRAF gene are present in approximately 50% of all melanomas. The most common mutation of this gene is V600E (90%). Mutation in the BRAF gene leads to a 500-fold increase in BRAF kinase activity and constitutive activation of downstream kinases in the RAS/ RAF/MEK/ERK pathway, which promotes proliferation and survival of tumour cells. The introduction of BRAF inhibitors and their subsequent combination with MEK inhibitors significantly improved progression-free survival and overall survival in patients with BRAF-mutated advanced melanoma. In daily clinical practice, we can use one of the three approved combinations of BRAF/MEK inhibitors (dabrafenib + trametinib, encorafenib + binimetinib,vemurafenib + cobimetinib), which are similar in terms of efficacy but differ slightly in their toxicity profile. Here, we present data mainly from randomised phase III trials encompassing the efficacy and safety profile of these approved BRAF/MEK inhibitor combinations.