The human epidermal growth factor receptor (HER) family of receptor tyrosine kinases controls critical pathways involved in epithelial cell differentiation, growth, division, and motility. Alterations and disruptions in the function of the HER-kinase axis can lead to malignancy. Many therapeutic agents targeting the HER-kinase axis are approved for clinical use or are in preclinical/clinical development. The ability to quantitatively image the HER-kinase axis in a noninvasive manner can aid in lesion detection, patient stratification, new drug development/validation, dose optimization, and treatment monitoring. This review summarizes the current status in multimodality imaging of the HER-kinase axis using PET, SPECT, optical, and MR imaging. The targeting ligands used include small-molecule tyrosine kinase inhibitors, peptides, proteins, antibodies, and engineered antibody fragments. EGFR and HER2 imaging have been well documented in the past, and imaging of HER3, HER4, HER heterodimers, and HER-kinase mutants deserves significant research effort in the future. Successful development of new HER-kinase-targeted imaging agents with optimal in vivo stability, targeting efficacy, and desirable pharmacokinetics for clinical translation will enable maximum benefit in cancer patient management.