A BRAF somatic mutation at residue 600 of the BRAF protein (BRAFV600E) is highly prevalent in papillary thyroid carcinomas (PTC). This mutation occurs in approximately 44% (from 29% to 83%) of PTC depending on the different studies. BRAFV600E is almost always found in PTC with a papillary or a mixed follicular/papillary architecture, being rarer in other subtypes of PTC. The discovery of the BRAFV600E mutation in tissue and fine-needle aspiration (FNA) is diagnostic for PTC and has been frequently associated with worse clinical prognosis. However, some studies failed to reveal this prognostic association. Transcriptional and post-transcriptional modulation of PTC with a BRAF mutation has been evaluated in some recent studies. Current therapeutic approaches targeting BRAF are being tested in clinical trials, particularly in more aggressive PTC. In this review, we will first discuss the diagnostic value of a BRAF mutation for PTC diagnosis. The prognostic role of a BRAFV600E mutation is then outlined and discussed in the context of other well-accepted clinicopathological prognostic parameters for PTC (age, gender, pTNM stage, histological subtype). Finally, the currently and potentially used treatments targeting BRAF in patients with PTC are presented.