AXL is a member of the TAM family, a receptor tyrosine kinase (RTK) subfamily composed of AXL, TYRO-3, and MER. Its main ligand is the vitamin K-dependent protein named growth arrest-specific gene 6 (Gas6). AXL is abnormally activated in many cancers by protein overexpression, point mutations, and gene fusions. The Gas6-AXL axis contributes to tumor progression, invasion, metastasis, and resistance both to chemotherapeutic and targeted anticancer therapies in a wide variety of cancers. In this review, we describe the biology of AXL, review diverse mechanisms of activation and the established and putative roles of AXL as a biomarker and therapeutic target in cancer therapy. Pre-clinical and clinical data for anti-AXL therapies to date are also summarized. © Springer Science+Business Media New York 2017. All rights reserved.