Protein tyrosine kinase (PTK) is considered as one of the main signaling catalysts during the transduction of cell signal. The role of PTK is to transfer the ATP-γ-phosphate to the tyrosine moiety in the targeted protein. This, in turn, resulted in many cellular processes, including; phosphorylation, controlling cell growth, regulation of the cell differentiation, apoptosis and many other cellular processes. Accordingly, any faulty expression of PTK however, resulted in faulty cell multiplication. Nowadays, various PTKs are utilized as targets for the treatment of cancer. The mechanism by which the tyrosine kinase inhibitors (TKIs) act as antitumor can be simplified as the TKIs prevent the ATP from reaching its binding site by competitory mechanism. This in turn will inhibit the phosphorylation of tyrosine kinase leading to suppress the tumor cell proliferation. TKIs have gained a great attention by researchers leading to discover many successful therapies, nevertheless, there are always challenges to be tackled. In this work, the authors summarize the mechanism of TKIs, highlighted the successes and drawbacks of TKIs for anticancer therapies.