Imaging of αvβ3 expression in malignant diseases has been extensively studied in the last years, mainly because the level of integrin αvβ3 expression might be a surrogate parameter of angiogenic activity. Most studies have been performed using preclinical tumor models but recently first results if imaging αvβ3 expression in patients have been published. The first approach used was the radiotracer approach with tracers for positron emission tomography (PET) like [(18)F]Galacto-RGD or tracers for single photon emission computed tomography (SPECT) like [(99m)Tc]NC100692. In this article we will focus on the experimental design and methodology of PET imaging of αvβ3 expression with the tracer [(18)F]Galacto-RGD. Common difficulties and pitfalls in image acquisition and interpretation will be discussed. Finally, the performance of PET will be compared to other methods of imaging of αvβ3 expression, like magnetic resonance imaging, ultrasound, or optical imaging.