The receptor tyrosine kinase FLT3 is an important regulatory molecule in hematopoiesis and is expressed on the blasts in most cases of acute leukemia. Activating mutations of this receptor are present in roughly 30% of acute myeloid leukemia (AML) patients and are associated with a distinctly worse clinical outcome. Efforts to target this mutation and improve out-comes in this subgroup of AML patients have led to the investigation of several novel small-molecule FLT3 tyrosine kinase inhibitors. These compounds derive from a wide variety of chemical classes and differ significantly, both in their potency and in their selectivity. In this review, we discuss the results of preclinical, clinical, and correlative laboratory studies of FLT3 inhibitors in demonstrating how this field represents a truly translational enterprise with multiple ongoing interactions between the laboratory and the clinic.