Over the last decade, investigators have developed a clearer understanding of the genetic alterations underlying thyroid carcinogenesis. A number of biomarkers involved in the pathogenesis of differentiated thyroid cancer have undergone intensive study, not only for their role in tumorigenesis, but also for their potential utility as diagnostic and prognostic indicators and therapeutic targets. This review summarizes the current literature surrounding BRAF and its significance in thyroid cancer. Further, we discuss how molecular analysis can be integrated into management algorithms for thyroid nodules and papillary thyroid cancer. We also review what is known, to date, about the association of BRAF and papillary microcarcinoma as well as using targeted therapies for BRAF as adjuvant treatment for metastatic papillary thyroid cancer.