This thesis describes fibroblast growth factor signaling in the development of resistance to tyrosine kinase inhibitor therapy in solid and hematologic malignancies, and in the maintenance of cancer-protective bone marrow stroma. Cell-extrinsic protection is emerging as a universal concept in cancer therapy. This promises to revolutionize the approach to targeted therapy, which previously centered on sequential employment of single inhibitors, or on drug combinations targeting several cell-intrinsic oncogene-activated pathways.