Biomedical and pharmaceutical research takes a lot of time, requires considerable money, effort, and the involvement of a huge number of scientists. Furthermore, it is still virtually impossible to conduct scientific research without the involvement of laboratory animals. On World Day for Laboratory Animals, we delve into the history of the issue and find out if modern technologies can replace the mice, rats, and fish used in experiments. Animal research has been conducted since ancient times—records of such experiments exist from Hippocrates and Galen, considered the founders of modern medicine. Galen, who lived in the 2nd century AD, is even called the father of vivisection—a term used for operations on live animals. Initially, animals were used to gain knowledge about anatomy and to practice surgical skills, but from the 19th century, they began to be actively used as subjects for studying physiology, the nature of diseases, and evaluating the effects of various drugs. Ivan Pavlov studied conditioned reflexes in dogs, Ivan Sechenov studied the processes of nervous excitement and inhibition in frogs, and Louis Pasteur studied the course of anthrax in sheep. Russian physiologist Ivan Pavlov with assistants and listeners at the Military Medical Academy. By the 20th century, the scale of animal experiments had become even more impressive. There is a viewpoint that all scientific achievements in the field of medicine in the 20th century would have been impossible without the participation of laboratory animals. Thanks to them, insulin was isolated, vaccines against leprosy were developed, many antibiotics were created and tested, and animal experiments allowed the creation of genetically modified organisms and the cloning of a mammal. Animals have contributed (and continue to contribute) not only to such revolutionary events as the cloning of Dolly the sheep but also to the process of creating most drugs. For example, assessing the toxicity of medicinal products—an essential step in testing new drugs—is impossible without animals. Is it possible to do away with animal experiments? The number of animals is indeed impressive—according to one study, 100 million individuals are used annually in research. These include not only mice, rabbits, frogs, which immediately come to mind, but also worms, zebrafish, naked mole-rats, monkeys, pigs, dogs, guinea pigs, and many other species. Most animals are bred specifically for experiments in the necessary quantities, and many lines carry certain mutations that simplify the conduct of experiments. For example, cancer drugs are tested on animals prone to tumor formation, and diabetes drugs are tested on those suffering from the disease. Scientists believe that it will not be possible to completely abandon our smaller brethren—alternative models can only partially replace them, as recreating such complex multicellular structures with complex physiology under artificial conditions is virtually impossible. Mini-organs: One of the promising directions is the creation of mini-organs intended for drug testing. These are tiny structures grown in laboratory conditions—hearts, kidneys, liver—consisting of cells and tissues characteristic of that organ. Such organoids are generally not capable of performing all the functions that full organs can, but they can "react" to one drug or another. One of the recent developments is the "mini-brain," grown at the Institute of Cytology and Genetics in Novosibirsk. Organoids will be used to study the impact of mutations on brain development and the emergence of various pathologies. Plant-based test system: Another approach is to use plants for drug testing. All cellular components were removed from spinach leaves, and the remaining "scaffold" was used as an analog of the vascular system. Researchers successfully tested their system by first introducing an artificial clot into the plant "vessel," then nanoparticles carrying a medicinal drug. The clot was successfully dissolved, the vessel's lumen freed, and the test system demonstrated its functionality. Phantom animals: Replacing real mice with three-dimensional models was conceived at Tomsk Polytechnic University. Phantom rodents were printed on a 3D printer. The printed animals are quite realistic—they have skin, a skeleton, and some internal organs, such as lungs, brain, and spinal cord. These mice are intended to optimize the conduct of radiation therapy for cancer diseases, and the use of phantoms will help work out all the parameters of radiation before treating a patient. Alternative models are becoming more numerous and are being implemented more widely; organs-on-chips are considered the most promising approach. However, they are not yet capable of completely replacing animal experiments. This will not happen until in vitro experiments, that is, experiments in a test tube, become so perfect that they are fully identical to living organisms. It is possible that this will occur in our century. For now, however, the "youngest scientific collaborators" continue to perform their important work, without which the emergence of new drugs and therapeutic approaches—essentially safeguarding the life and health of each of us—would not be possible.