Despite the fact that the microscope was born as a compound of two or more lenses, the protagonist of the earliest research on insects, worms, and tiny animals invisible to the naked eye was the simple microscope, which provided higher magnification at greater resolution.

The Dutchman Antoni van Leeuwenhoek built some 150 microscopes consisting of a single, tiny double-convex lens. Nine of his microscopes survive. The best of these has a magnification power of about 270 diameters: but some details in his drawings suggest that he possessed even more powerful ones, with which he was able to observe red blood cells, spermatozoa, rotifers, and bacteria from 1677 onwards.

Even his compatriot Jan van Musschenbroek, for entomological research, used a simple microscope mounted on an articulated arm that proved extremely effective. Adopted by Abraham Trembley, it established itself as the "aquatic" microscope of choice for observing flora and fauna from the outside of a glass vessel. In 1740, it enabled the Genevan naturalist to observe, for the first time, not only the behavior of the "freshwater polyp" but also its surprising capacity to regenerate amputated parts.

The next development in the simple microscope was Pieter Lyonet's "anatomical tablet," used, among others, by Lazzaro Spallanzani for minute dissections. However, for entomological research, the Italian naturalist probably used the microscope designed by James Wilson and built by John Cuff around 1742, also called "portable" or "pocket" microscope. A compound microscope only in appearance, this model enabled—among other things—Spallanzani in 1773 to discover tardigrades and their ability to experience repeated death/revival cycles. The phenomenon, now called anabiosis, marked one of the major turning points of 18th-C. theoretical biology.