Acute encephalopathy secondary to targeted therapy with BRAF inhibitors is uncommon. There are few case reports in patients with metastatic melanoma who received treatment with dabrafenib and trametinib, and developed acute confusion. The encephalopathy appears to resolve after the discontinuation of offending drug, with patient returning to their baseline mentation and functional ability. The mechanism of the encephalopathy has been unclear. Unlike posterior reversible encephalopathy syndrome, which has been reported with vemurafenib and cobimetinib combination in melanoma patients, there are generally no acute imaging abnormalities observed (e.g. on computed tomography and magnetic resonance imaging brain scans). We report a case of acute encephalopathy in a patient with BRAF mutated metastatic lung cancer due to dabrafenib and trametinib treatment. With the increasing use of targeted therapies in lung cancer treatments, it is important for clinicians to be aware of potentially toxic effects of novel treatments.