The rapid advent of technology in recent years has resulted in a substantial increase in our knowledge of the molecular underpinnings of thymic epithelial tumors. In addition to previously described chromosomal aberrations and alterations in DNA methylation, genome sequencing has helped unravel hitherto unknown mutations in these tumors. Attempts are also being made to develop gene signatures to help in the identification of patients likely to benefit from adjuvant therapy. Some of the recently identified genetic alterations have the potential to serve as targets for biological therapy, thus opening newer avenues for treatment of thymic epithelial tumors and increasing the number of effective options for treatment of recurrent or refractory disease.