Activities involving the use of animals in research date back to more than 2,000 years BCE. At the time, animals were used in surgeries and comparative studies aimed at elucidating the mysteries surrounding the functioning of living organisms. Over the centuries, use has become more frequent, with the improvement of the techniques used, but still without any concern for animal suffering, well-being, or ethical issues. It was only around the 19th century, in England, that questions about this began to arise. Since then, animal protection bodies have been created, laws have been enacted and, in 1959, Russell and Burch created the principle of the 3Rs (replacement, reduction, and refinement), assumptions that guide teaching and research activities involving animals to this day. Recent data show that the number of animals used in research reached 192.1 million in 2015 worldwide, a number that, in 2005, was approximately 127 million. The present work aims to describe the historical evolution of the use of animals in research activities around the world and the protection mechanisms involved so that, from this, we can understand how we evolved to the significant number of scientific productions involving animals today.