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Abstract Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that plays important regulatory roles in several basic cellular activities. During normal development, FAK is a critical mediator of the integrin signaling cascade, which modulates cell proliferation, apoptosis, adhesion, spreading and migration. Importantly, FAK overexpression is found in a large number of cancer types and FAK expression levels generally correlate with increased tumor malignancy. Though FAK has been a popular potential target for treatment of solid tumors, its roles in leukemias and lymphomas have not been well defined. Here, I briefly summarize the multifaceted functions of FAK in tumor progression, and discuss current efforts and exciting future directions of using RNAi-mediated knockdown of FAK as a potential therapy against leukemia and lymphomas.