Prostate cancer is an extremely complex multifactorial disease that poses a major health problem to men worldwide. Metastasis to distant sites is the underlying basis of poor prognosis and high fatality in patients with prostate cancer. Numerous protein kinase families are associated with prostate cancer tumorigenesis, and their members either individually and/or collectively drive its progression. SFKs belonging to the nonreceptor tyrosine kinase family play critical roles in signaling pathways that are frequently altered in cancers. In prostate cancer, these kinases activate pathways linked to increased invasiveness, angiogenesis, metastasis, and poor response to known therapeutics. A number of SFK inhibitors have demonstrated immense promise in preclinical cancer models and are currently in different stages of clinical trials. In this chapter, we discuss the role of these kinases in prostate cancer tumorigenesis and the clinical relevance and challenges associated with the usage of SFK inhibitors in clinics. © 2022 Elsevier Inc. All rights reserved.