Animal experimentation requires a solid and rational moral foundation. Objective and emphatic decision-making and protocol evaluation by researchers and ethics committees remain a difficult and sensitive matter. This article presents three perspectives that facilitate a consideration of the minimally acceptable standard for animal experiments, in particular, in tissue engineering (TE) and regenerative medicine. First, we review the boundaries provided by law and public opinion in America and Europe. Second, we review contemporary moral theory to introduce the Neo-Rawlsian contractarian theory to objectively evaluate the ethics of animal experiments. Third, we introduce the importance of available reduction, replacement, and refinement strategies, which should be accounted for in moral decision-making and protocol evaluation of animal experiments. The three perspectives are integrated into an algorithmic and graphic harm-benefit analysis tool based on the most relevant aspects of animal models in TE. We conclude with a consideration of future avenues to improve animal experiments.