Antibody-drug conjugates (ADCs) represent a major advance in the treatment of acute lymphoblastic leukemia (ALL). CD22 expression, seen in majority of patients with B-lineage ALL, is an ideal target for ADCs. Inotuzumab ozogamicin is an ADC comprised of a humanized IgG4 monoclonal antibody covalently linked to calecheamicin. Inotuzumab ozogamicin has shown promising single-agent activity in patients with ALL and in CD22 positive non-Hodgkin lymphoma. Studies exploring the combination of inotuzumab ozogamicin with chemotherapy are ongoing.