The rodent grip strength test was developed decades ago and is a putative measure of muscular strength. This test has been included in the functional observational battery (FOB) to screen for neurobehavioral toxicity, and changes in grip strength have been interpreted as evidence of motor neurotoxicity. Despite its widespread use, questions remain about what the grip strength test actually measures. In this study, potential confounders of the grip strength test were identified and tested, including operational parameters, disruption of peripheral sensory function and changes in body weight. Operational parameters (sampling rate, system type and trial angle but not trial speed) had dramatic effects on grip strength data. Doxorubicin (DX, 10 mg/kg iv) was used to cause sensory impairment. It decreased forelimb and hindlimb grip strength (by 27% and 32%, respectively, compared with controls), an effect that was correlated with degeneration of peripheral and central sensory components (distal tibial and sural nerves, dorsal funiculus of the spinal cord and dorsal, but not ventral, spinal roots). Feed restriction-induced loss of body weight (26% compared with controls) and muscle mass (20% compared with controls) reversibly decreased both forelimb and hindlimb grip strength (18% and 17%, respectively, compared with controls). Ignoring these confounding factors could potentially lead to increased data variability and inconsistency within single studies, across studies and in historical control data sets. To assist in data interpretation and evaluation of grip strength results, it is suggested that exact conditions of application of the test be reported in greater detail. Furthermore, given that the grip strength test can be influenced by factors other than true muscular strength, use of the term grip performance is proposed to better reflect the apical nature of this test.