Originally the term "yellow flags" was used to describe psychosocial prognostic factors for the development of disability following the onset of musculoskeletal pain. The identification of yellow flags through early screening was expected to prompt the application of intervention guidelines to achieve secondary prevention. In recent conceptualizations of yellow flags, it has been suggested that their range of applicability should be confined primarily to psychological risk factors to differentiate them from other risk factors, such as social and environmental variables. This article addresses 2 specific questions that arise from this development: (1) Can yellow flags influence outcomes in people with acute or subacute low back pain? and (2) Can yellow flags be targeted in interventions to produce better outcomes? Consistent evidence has been found to support the role of various psychological factors in prognosis, although questions remain about which factors are the most important, both individually and in combination, and how they affect outcomes. Published early interventions have reported mixed results, but, overall, the evidence suggests that targeting yellow flags, particularly when they are at high levels, does seem to lead to more consistently positive results than either ignoring them or providing omnibus interventions to people regardless of psychological risk factors. Psychological risk factors for poor prognosis can be identified clinically and addressed within interventions, but questions remain in relation to issues such as timing, necessary skills, content of treatments, and context. In addition, there is still a need to elucidate mechanisms of change and better integrate this understanding into the broader context of secondary prevention of chronic pain and disability.