Fatigue crack growth in natural rubber is studied using fracture mechanics concepts and an extension of Griffith's criterion. The effects of load ratio, temperature, and environment are examined. It appears that, for cycles without compression, a mean stress in tension improves the fatigue behavior by inducing crystallization, whereas a minimum stress in compression greatly damages the material. Tests under inert atmosphere show that, in addition to the mechanical damage, an important chemical damage due to oxygen is present. The fatigue cracking of natural rubber is also approached studying the influence of damage mechanisms in relation to microstructural aspects. In this way, SEM observations of fracture surfaces show a marked dependence on crack growth rate, load ratio, temperature, and environment. For high growth rates, we observe some fatigue striations, and we notice a microscopic mechanism for formation of tongue structure, which is highly dependent on gaseous oxygen and typical of natural rubbers.