Nearly every prescription medicine available today has been tested on animals. However, animal experimentation remains one of the most contentious aspects of biomedical research. While scientists strive to apply the replacement, reduction, and refinement principles, the use of animals in research has been increasing steadily due to a lack of universally accepted alternatives. Many animal rights groups argue that this shortage of alternatives is due to inadequate effort to create them. To many animal activists, the only morally permissible way forward is the total abolition of animal use in research. They see the legal personhood for nonhuman sentient animals, starting with nonhuman primates, as a means to an end. This commentary revisits the moral justification for animal experimentation from a contemporary philosophical viewpoint. It also discusses the concept of legal personhood for nonhuman animals and describes evolving alternatives that have the potential to replace animal experimentation.