VEGFs and a respective family of tyrosine kinases receptors (VEGFRs) are key proteins modulating angiogenesis, the formation of new vasculature from an existing vascular network. There has been considerable evidence in vivo, including clinical observations, that abnormal angiogenesis is implicated in a number of disease conditions, which include rheumatoid arthritis, inflammation, cancer, psoriasis, degenerative eye conditions and others. Antiangiogenic therapies based on inhibition of VEGF/VEGFR signalling were reported to be powerful clinical strategies in oncology and ophthalmology. Current efforts have yielded promising clinical data for several antiangiogenic therapeutics. In this review, the authors elucidate key aspects of VEGFR signalling, as well as clinically relevant strategies for the inhibition of VEGF-induced angiogenesis, with an emphasis on small-molecule VEGFR inhibitors.