Only a handful of radiolabeled antibodies (Abs) have gained US Food and Drug Administration (FDA) approval for use in clinical oncology, including four immunodiagnostic agents and two targeted radioimmunotherapeutic agents. Despite the advent of nonimmunogenic Abs and the availability of a diverse library of radionuclides, progress beyond early Phase II radioimmunotherapy (RIT) studies in solid tumors has been marginal. Furthermore, [18F]fluorodeoxyglucose continues to dominate the molecular imaging domain, underscored by a decade-long absence of any newly approved Ab-based imaging agent (none since 1996). Why has the development of clinically successful Abs for RIT been limited to lymphoma? What obstacles must be overcome to allow the FDA approval of immuno-positron emission tomography (immuno-PET) imaging agents? How can we address the unique challenges that have thus far prevented the introduction of Ab-based imaging agents and therapeutics for solid tumors? Many poor decisions have been made regarding radiolabeled Abs, but useful insight can be gained from these mistakes. The following review addresses the physical, chemical, biological, clinical, regulatory and financial limitations that impede the progress of this increasingly important class of drugs.