Gesner's Historia animalium is considered one of the starting points of modern zoology; it contains 4,500 pages and nearly 1,000 woodcuts, some by Albrecht Dürer. The illustrations are the first original zoological illustrations, and the first naturalistic representations of animals to be published in print. His encyclopedic work includes the names of the known animals in ancient and modern languages, together with a mass of information regarding them. Vol. 1 on four-footed mammals was published in 1551; Vol. 2 on egg-laying quadrupeds (reptiles and amphibia) was issued in 1554; Vol. 3. on birds in 1555; Vol. 4 on fish and aquatic animals in 1558. Vol. 5 on snakes and scorpions was issued posthumously in 1587.

In this work Gesner attempted to build a connection between ancient knowledge of the animal world, and what was known at his time. He compiled it from ancient and medieval texts, including ancient naturalists like Aristotle, Pliny the Elder, and Aelian, and even the medieval Physiologus. To this information he added his own observations, and those of his correspondents, in an attempt to formulate a comprehensive description of the natural history of animals, with detailed descriptions of their daily habits and movements, and their uses in medicine and nutrition.

The work was translated into German and published by Froschauer between 1557 and 1563. Portions were translated into English by Edward Topsell as The historie of four-footed beasts. London, 1607, and The historie of serpents (1608). These English translations were combined as The history of four-footed beasts and serpents (1658).