Since most solid tumor growth depends on angiogenesis, non-invasive imaging of tumor angiogenesis can allow for much earlier diagnosis and better prognosis of cancer, as well as more accurate treatment monitoring, which will eventually lead to personalized molecular medicine. CD105, also known as endoglin, is required for endo-thelial cell proliferation. The currently accepted standard method for quantifying tumor angiogenesis is to assess microvessel density based on CD105 staining, which has been shown to be an independent prognostic factor for survival in patients of almost all solid tumor types. In this review, we will summarize the progress to date on multimo-dality molecular imaging of CD105 expression during tumor angiogenesis which includes targeted contrast-enhanced ultrasound, molecular magnetic resonance, near-infrared fluorescence, single-photon emission computed tomography, and positron emission tomography. Although molecular imaging of CD105 expression is surprisingly understudied, non-invasive imaging of CD105 expression has already been achieved with every single molecular imaging modality. In the future, significant research effort should be directed towards non-invasive visualization of CD105 expression, such as quantitative imaging, the use of long-lived isotopes for antibody-based imaging, development of peptide, small molecule, or antibody fragment-based imaging agents, multimodality imaging of CD105 expression with a single agent, the application of nanotechnology, among others.