Purpose/Hypothesis: Sarcopenia is an age-related decline in skeletal muscle mass and strength and a major cause of decreased physical function contributing to frailty in the elderly. Sarcopenia is a prominent impairment in a variety of chronic diseases seen by physical therapists. The purpose of this study was to determine the impact of lower extremity (LE) muscle strength (sarcopenia) and its relationship to physical frailty in diabetic neuropathic (DN), elderly obese (EO), and elderly non-obese (EN) individuals. Subjects: Fifty-three DN subjects (37 men, 16 women; age 54±10 years, mean BMI= 32 ± 6; duration of DM 16±11years); 29 EO subjects (12 men, 17 women, age 70±4 years, BMI = 38±5); and 95 EN subjects (25 men, 70 women, age 80±7 years, BMI = 25±6) were studied. Materials/Methods: All impairment measurements were collected during a single session. The 9-item physical performance test (PPT) was used as an objective assessment of physical frailty. Peak torque of the quadriceps, hamstrings, plantar flexors, and dorsiflexors was assessed at 3 speeds with an isokinetic dynamometer to determine muscle strength and severity of sarcopenia. Mean ± sd were calculated for each cohort and compared using oneway ANOVA. Univariate and multivariate (age, BMI, and peak torque of the quadriceps, hamstring, dorsiflexors, and plantarflexors) regression analyses were performed for the entire sample (pooled) and in each cohort separately to determine the best predictors of physical frailty (total PPT score). Results: The mean PPT score was 26±7 in the DN group, 27±3 in the EO group and 22±6 in the EN group. (F=15.3, p<0.00). Regression analyses demonstrated age, BMI, quadriceps and dorsiflexor strength best predict PPT in DN group (r2=0.501, p<0.03), while quadriceps, dorsiflexor and plantar flexor strength best predict PPT in EN group (r2=0.304, p<0.04). In the EO group, BMI best predicts PPT (r2=0.146, p<0.05), while strength of LE muscle groups did not predict total PPT score. Conclusions: Sarcopenia is a common pathogen that occurs with aging and predicts physical frailty accompanying several chronic diseases including diabetes mellitus with peripheral neuropathy and to a lesser extent obesity. The results of this study demonstrate that BMI and excess body fatness (obesity) may contribute to physical frailty in EO participants more than LE muscle strength. Our results also suggest that strength assessment of several muscle groups of the LEs predict physical frailty to a larger extent than a single muscle group for individuals with generalized sarcopenia. Clinical Relevance: Our study suggests there are likely many contributors to physical frailty among individuals seen routinely by physical therapists. A more comprehensive and thorough understanding of the role of sarcopenia in physical frailty may help determine optimal rehabilitation strategies in the amelioration of sarcopenic skeletal muscles. Supported by the NIH T32 HD 007434, RO1 DK 59224, RO1 AG 025501.