Overexpression of the epidermal growth factor receptor tyrosine kinase (EGFR-TK) has been documented in numerous human cancers of epithelial origin, and was found to correlate with resistance to treatment and poor prognosis. Recognizing the central role that this receptor plays in cancer development and progression, various approaches have been developed to target it in order to more specifically eradicate cancer cells. These methods include, among others, low-molecular weight inhibitors of the TK domain that are commonly designed to treat those tumors that overexpress the EGFR. Nevertheless, no currently available assay provides non-invasive, longitudinal and sensitive quantitation of receptor levels in tumors so as to better identify candidate patients for EGFR-targeted therapies. Hence, attempts have been made to develop radiolabeled molecular imaging agents as potential bioprobes to quantitatively monitor treatment efficiency. Such EGFR-targeted bioprobes could not only improve patient selection and treatment monitoring, but also allow a direct delivery of radionuclides for radiotherapy. In this review, the role that EGFR plays in cancer development and therapy is briefly presented, followed by a short review of prominent milestones in the development of EGFR-TK inhibitors. These inhibitors constitute the fundamental core structure for the development of radiolabeled probes to visualize the EGFR in vivo. The considerations that need to be taken into account for the development of such probes will be presented, along with a critical examination on the progress that has been made thus far in the field.