Guido Panerai, the grandson of the founder, knew how to use an invention from 1914 for his products: the special mixture of zinc sulfate and radium bromide he named it Radiomir and had it patented in 1916. This luminous substance enabled the reading of the dials even in the deep waters, in the dark and under the worst visibility conditions. The reward soon followed. Panerai was then charged with the production of wrist watches and this was the birth of Panerai Radiomir. Shortly after Panerai supplied the Royal Navy with diving watches, depth knives, signaling devices, and marine compasses worn on the wrist. In the first years, the Radiomir watches contained movements from the Cortébert company which were manufactured at Rolex. Thanks to its indestructibility and its unique appearance, the Radiomir became a cult watch. Officine Panerai responded and produced re-editions of the watch from 1993 onwards. The Panerai Radiomir reference 3646 with a hand-winding movement calibre Rolex 618 is a legendary military watch, which co-founded the reputation of the brand Panerai. It is also known under the name "3646 Combat Swimmer" or "Combat Swimmer Panerai". The Radiomir, developed as a prototype in 1936 and manufactured from 1938, was the first professional diving watch, ever. Shortly before the beginning of the Second World War Panerai developed ten prototypes of the "Radiomir" model with 47mm pillow-shaped housing for the special units of the Italian Marina Militare. A documentary film from the year 1944 and pictures according to the German combat swimmer group got some Panerai copies, which they used. The models on the engravings of the names in the floor cover of the watches, for collectors, are an important feature.

In the 90s, the special "Slytech" was also created for the American actor Sylvester Stallone, which contributed significantly to the popularity of the brand. The Hollywood star had commissioned Officine Panerai to create the Submersible. In each of the films "Daylight", "Expendables" and "Rambo 4" the big watch lover Stallone was wearing a timepiece from the house Panerai. Since 2002, Panerai has been developing and manufacturing watches in the own manufacture company in Neuchâtel, Switzerland. The first "genuine" manufacture calibre was created here after four years of development, the P.2002 with manual winding, GMT function and 8 day power reserve. This movement was built exclusively in the Panerai Radiomir 8 Days GMT and in the Luminor 8 Days GMT. In 2005, the two highly regarded Italian brands, Ferrari SpA and Officine Panerai signed a five-year contract for the manufacture and sale of high-quality watches under the brand name "Ferrari Engineered by Officine Panerai".