The aim of this study was to compare eight methods for the estimation of the image-derived input function (IDIF) in [(18)F]-FDG positron emission tomography (PET) dynamic brain studies. The methods were tested on two digital phantoms and on four healthy volunteers. Image-derived input functions obtained with each method were compared with the reference input functions, that is, the activity in the carotid labels of the phantoms and arterial blood samples for the volunteers, in terms of visual inspection, areas under the curve, cerebral metabolic rates of glucose (CMRglc), and individual rate constants. Blood-sample-free methods provided less reliable results as compared with those obtained using the methods that require the use of blood samples. For some of the blood-sample-free methods, CMRglc estimations considerably improved when the IDIF was calibrated with a single blood sample. Only one of the methods tested in this study, and only in phantom studies, allowed a reliable calculation of the individual rate constants. For the estimation of CMRglc values using an IDIF in [(18)F]-FDG PET brain studies, a reliable absolute blood-sample-free procedure is not available yet.