Book excerpt: With the persisting need of animal experimentation for fundamental and applied research, the relevance and importance of the 3Rs Principle cannot be ignored. The 3Rs Principle was put forward over 50 years ago, providing an essential framework for more humane animal experimentation in research. In this half-century the research landscape within which this principle is applied has dramatically changed and evolved, with ever more emerging venues to explore for 3Rs advancement and implementation.