Here, we provide an overview of the diverse approaches that have been taken to date to target NK-92 cells to various hematological malignancies and solid tumors, summarize preclinical in vitro and in vivo studies with special emphasis on ErbB2 (HER2)-specific CAR NK-92 cells (NK-92/5.28.z) that are ready to enter clinical trials, and discuss general advantages and challenges associated with the use of CAR NK-92 cells as an off-the-shelf cellular therapeutic. The gene discussed is ERBB2; the disease is hematologic disorder.