The connection between work-related exposures and the onset of back injury or pain is complex and not clearly understood. This paper raises design issues related to the planning and conduct of cohort studies of industrial low back pain (or injury)(LBP), with care given to definition and measurement of exposure and outcome events. These issues include sample size, outcome definition, study biases, and practical considerations when seeking and maintaining company collaboration with a research effort. Without resolving these issues, the authors conclude: (1) cohort studies of worksite-based LBP are needed to elucidate the causal associations between work tasks and LBP onset, (2) both acute and cumulative exposures should be assessed as risk factors for low back injury or pain, and (3) attention should be paid to the planning of such studies and minimization of potential biases that can limit the validity of the results. These design issues will benefit researchers and companies engaged in the planning and conduct of cohort studies of industrial LBP.