The limited data suggest that exposure to microgravity decreases muscle strength in humans and muscle mass in lower mammals. Whether these adaptations are a result of the lack of gravity per se and/or of the associated unweighting of the neuromuscular system is not clear. Several earth based models have been used to address the effect of unweighting. Bedrest eliminates body weight bearing of both lower limbs. Unilateral lower limb suspension (ULLS), where all ambulatory activity is performed on crutches with an elevated sole on the shoe of one foot, has recently been used to unweight one lower limb. The results from studies using these two models support their efficacy. The decrease in strength of the knee extensors (KE), for example, after four to six weeks of bedrest, ULLS or space flight is 20 to 25 %. The results from the earth based studies show that this response can be attributed inpart to a decrease in cross-sectional area of the KE which reflects muscle fiber atrophy. The results from the ground based studies also support the limited flight data, and show that reductions in strength are larger in lower than upper limb and in extensor than flexor muscle groups. They also raise issue with the generally held concept that postural muscle is most effected by unweighting. Slow-twitch fibers in lower limb muscles of mixed fiber type composition and muscle composed mainly of slow-twitch fibers do not preferentially atrophy after bedrest or ULLS. Taken together, the data suggest that unweighting causes remarkable adaptations in the neuromuscular system of humans. It should be appreciated, however, that this area of research is in its infancy. Because of the limited access of biological research to long term space flight, it is critical that future studies using these models be conducted in an effort to plan the most effective flight research.