A key implication of the cancer stem cell model is that for a cancer therapy to be curative, it is imperative to eliminate the cancer stem cells (CSCs) that drive tumor progression. The California Institute for Regenerative Medicine is supporting two novel approaches that target CSCs, one an antibody-mediated immunotherapy targeting CD47 and the other an antibody targeting ROR1. This article summarizes the evidence that CSCs are targeted and discusses the results of early clinical trials within the context of the CSC model.