Rodents can transmit a variety of serious zoonotic diseases, some of which have historically caused more deaths than wars.

Plague is the most famous rodent-borne disease, caused by the bacterium Yersinia pestis transmitted by rodent fleas — the Black Death of the Middle Ages wiped out an estimated 30–60% of Europe's population in the 14th century.

Modern plague still exists, with the WHO reporting hundreds to thousands of cases annually, primarily in parts of Africa and Asia.

Leptospirosis is transmitted through contact with water or soil contaminated with infected rodent urine, causing high fever, severe headache, and liver and kidney failure.

Hantavirus pulmonary syndrome (HPS) is transmitted by inhaling aerosolized virus particles from the urine, feces, or saliva of infected rodents, with a case fatality rate as high as 30–40%.

In China, hemorrhagic fever with renal syndrome (HFRS) is a significant rodent-borne disease in winter and spring.

Salmonellosis — the intestines and feces of rodents carry various Salmonella serotypes, contaminating food and causing acute gastroenteritis.

Rat-bite fever — caused by infection with Streptobacillus moniliformis or Spirillum minus after a rodent bite; after the wound heals, patients suddenly develop recurrent fever and rash.

The core strategy for preventing these diseases is to prevent rodents from entering living spaces — seal all possible entry points, properly store food and garbage, and when cleaning rodent droppings, wear a mask and gloves and moisten droppings with disinfectant to prevent inhaling virus-laden dust.