The human epidermal growth factor receptor 2 (HER-2) is a key member of the HER family of receptor tyrosine kinases. Activation of HER-2 affects cell growth, proliferation, migration, adhesion, and survival. Due to its crucial role in carcinogenesis and tumor progression, HER-2 has been intensively investigated as a target for cancer therapy. The ability to quantitatively image HER-2 expression 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 state of understanding in multimodality imaging of HER-2 using positron emission tomography (PET), single photon emission computed tomography (SPECT), optical, and magnetic resonance (MR) imaging with HER-2 specific antibodies, antibody derivatives and affibodies as targeting ligands. Successful development of new HER-2 targeted imaging agents with optimal in vivo stability, targeting efficacy, and desirable pharmacokinetics for clinical translation will enable maximum benefit in cancer patient management.