Scientists have identified the impact of angiogenesis on tumor growth and survival. Among other efficient drugs, several small-molecule tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptor (VEGFR) have been developed and have already been integrated into the treatment of various advanced malignancies. This review provides a compilation of current knowledge on the pharmacokinetic aspects of all VEGFR-TKIs already approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and of those still under investigation. Additional information on substance metabolism, potential for drug-drug interactions (DDIs), and the need for dose adaptation in patients with predominant renal and/or hepatic impairment has been included. All TKIs introduced in this review were administered orally, allowing for easy drug handling for healthcare professionals and patients. For almost all substances, the maximum plasma concentrations were reached within a short period of time. The majority of the substances showed a high plasma protein binding and their excretion occurred via the feces and, to a lesser extent, via the urine. In most cases, dose adaptation in patients with mild to moderate renal or hepatic impairment is not recommended. Cytochrome P450 (CYP) 3A4 was found to play a crucial role in the drug metabolic processes of many compounds. In order to prevent unwanted DDIs, co-administration of VEGFR TKIs together with CYP3A4 inhibitors or inducers should be avoided. Throughout all TKIs, the data indicate high inter-individual variability. The causes of this are still unclear and require further research to allow for individualization of treatment regimens.