In 2011 and 2012, 147 patients in urban United States Community Health Centers who misused drugs, but did not meet criteria for drug dependence, received a brief intervention as part of a National Institute on Drug Abuse-funded clinical trial of a screening and brief intervention protocol. Potential study participants were identified using the World Health Organization (WHO) Alcohol, Smoking, and Substance Involvement Screening Test. Data gathered during brief interventions were analyzed using grounded theory strategies to identify barriers patients believed inhibited drug use behavior change. Numerous perceived barriers to drug use behavior change were identified. Study implications and limitations are discussed.