Study Design. Narrative review and discussion of the selected literature. Objectives. To discuss some important methodologic challenges in low back pain research in primary care. Summary of Background Data. Many methodologic problems must be confronted when conducting low back pain research. Some of these problems are back pain specific or specific to the primary care setting. Methods. Methodologic problems related to four research issues will be discussed: study designs, definition of low back pain, determinants of low back pain, and outcome assessment. Results. Two fundamentally different study designs are frequently used in low back pain research, namely observational studies and experimental studies. The definition of low back pain is typically restricted to a highly variable self-reported symptom, the sensation of pain in the back. There clearly is a need for an evidence-based classification system for low back pain. Because a tenable theoretical framework is lacking, it is difficult to know which determinants of low back pain should be quantified. Low back pain studies focus usually on health-related quality-of-life outcome parameters. The identification of the minimum clinically relevant changes for the most important outcome instruments needs further consideration. Conclusions. In years to come, low back pain researchers are challenged to overcome some of these (and other) problems to enhance the quality of low back pain research in primary care.