Chemical dependence, including nicotine, alcohol, prescription drugs, and illicit drugs, is one of the leading causes of morbidity and mortality in the United States. Primary care physicians and nurses routinely provide preventive health care and rely on routine screening to detect diseases and promote wellness. These primary care practitioners are in a unique position to assess and detect such dependence at its earliest stages. However, previous research indicates that little such screening is actually conducted. This literature review gathered and examined substance use screening instruments in four categories to assess their feasibility for use in primary care settings. Although substance use screening tools are available, most are not appropriate for screening in a primary care setting. There clearly remains a need for the development of a valid, reliable screening instrument that can be easily incorporated into the practices and procedures found in primary care settings.