Tyrosine kinase inhibitors (TKIs) are blockers of tyrosine kinase proteins which are known for the activation of signaling pathways especially in neoplastic cells. TKIs are among targeted anticancer medications that are available in the market. Imatinib was introduced in the late 1990s as the first TKI medicine in oncology, followed by gefitinib, erlotinib, sorafenib, sunitinib, dasatanib and the list of TKIs is being updated nearly every month. To review the safety, efficacy, and current clinical stage of TKIs in different malignancies, particularly leukemia, advanced gastrointestinal and breast cancer, whole literature over the last decade (2006 to 2017) were searched to find all related studies. Criticizing current data indicates that TKIs have shown better clinical outcome in terms of both safety and efficacy compared to conventional therapies. Meanwhile, regarding the results of available clinical trials, the best approach into maximizing the benefits of this novel targeting therapy and also minimizing the undesirable adverse effects, is to evaluate the pharmacogenetic data of patients before allocating these agents in their treatment setting.