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This chapter presents some considerations in order to foster debate and to place the issue of animal research in a context of the growing social, scientific and ethical debate. It shows that the timing is appropriate before the widespread introduction of a context that emphasized the use of animals for dealing with protection of human health and where alternative methods are brought up as real possibilities of scientific research. The chapter provides a description of the current international practices regarding the acceptance of alternative methods to animal testing and their situation. In fact, the process of validation of alternative methods is aimed at assessing the optimization, reproducibility and relevance of the method in order to be submitted to the regulatory agency and, become officially available for toxicological purposes. Optimization of existing systems is an important part of the strategy to accelerate the implementation of a mostly animal-free safety science, in addition to the more time-demanding development of entirely new methods.