The collection of books is based on his Paduan lectures, during which he deviated from common practice by dissecting a corpse to illustrate what he was discussing.

In the opening chapters, Vesalius "gives general aspects of bones and skeletal organisation, dealing with the differences in texture, strength, and resilience between bone and cartilage; explaining the complex differences between types of joints and reviewing some basic elements of descriptive techniques and terminology."

Here Vesalius describes the structure of the muscles, the agents used in creating movement by the body, and the material used to hold the joints together.

Vesalius was unfamiliar with the anatomy of pregnancy, which lead him to erroneously provide illustrations of a zonary (band-shaped) placenta and fetal membrane in the 1543 edition of De Fabrica; Vesalius does so relying on Galenic medicine which used canine reproductive organs rather than human female reproductive organs.

Galen, the prominent Greek physician, surgeon and philosopher in the Roman empire, had written on anatomy among other topics, but his work remained largely unchecked until the time of Vesalius.

The Fabrica rectified some of Galen's worst errors, including the notion that the great blood vessels originated from the liver.

Even with his improvements, however, Vesalius clung to some of Galen's errors, such as the idea that veins and arteries carried different respective types of blood.

It was not until William Harvey's work on the circulation of the blood (De Motu Cordis, 1628) that this misconception of Galen's would be rectified in Europe.

Vesalius had the work published at the age of 28, taking great pains to ensure its quality, and dedicated it to Charles V, Holy Roman Emperor.

The more than 250 illustrations are of great artistic merit and are generally attributed by modern scholars to the "studio of Titian" rather than Johannes Stephanus of Calcar, who provided drawings for Vesalius' earlier tracts.

The woodcut blocks were transported to Basel, Switzerland, as Vesalius wished that the work be published by one of the foremost printers of the time, Johannes Oporinus.

The success of Fabrica recouped the work's considerable expense, and brought Vesalius European fame, partly through cheap unauthorized copies.

[7] Therefore, in order to combat this opposition, Vesalius had to secretly take the bodies of executed criminals, a process which he explains in De Humani Corporis Fabrica.

De Humani Corporis Fabrica, a 2022 documentary film about the human body by Lucien Castaing-Taylor and Véréna Paravel, was named after the book series.