Among radionuclides usable for tumor therapy, α-particle emitters are characterized by a very high linear energy transfer (LET) resulting in a larger number of ionizations in a range corresponding to a cell diameter. Therefore, they can determine a stronger therapeutic effect compared to low LET β-particle emitters, producing their ionizations in a range up to many millimeters. In fact, because the distance between the two strands of DNA is almost the same as the distance between two ionizations of α-particles, DNA double strand breaks are induced with a high probability that finally cause cell death due to inefficient repair. Conversely, no therapeutic effect can be determined outside of concentrating sites. Therefore, the short range of α-emitters makes them powerful tools mainly when a therapeutic effect has to be reached in a restricted area, as in the elimination of minimal residual disease or in micro-metastases. Therapeutic efficacy of α-emitter radionuclides has been proven in numerous pre-clinical studies, but up to today only three main human studies are reported, including the treatment of myeloid leukemia by an anti-CD33 monoclonal antibody labelled by bismuth- 213 (213Bi), the therapy of patients with bone metastases from hormone-refractory prostate cancer by radium-223 (223Ra) and the loco-regional targeted radiotherapy with astatine-211(211At)-labelled anti-tenascin monoclonal antibody in patients with recurrent malignant brain tumours. The authors reviewed these human reported studies, evaluating perspectives, advantages and limitations of the targeted α-particle therapy.