Background: Prescription drugs, such as stimulants, opioid analgesics, anxiolytics, and sedatives, are frequently being used without a physician's prescription by college students, resulting in a rising epidemic. The literature has not yet examined the impact of one's social network in the use of these drugs, nor the co-occurrence of multiple prescription drugs. The current study investigated predictors of non-medical use of prescription drugs (NMUPD), in addition to the prevalence of NMUPD in college students' social networks. Methods: 279 undergraduates from a large southeastern university were recruited to participate in the study. Logistic regressions were conducted to examine the predictors of the respondent misusing prescription drugs in the past 12 months. Results: The number of close friends who misused prescription drugs predicted the respondent misusing prescription drugs in the past year (p<.05), after controlling for the respondent's own substance use. The misuse of prescription drugs by college students and their close friends is widespread: approximately one-fourth of the sample used prescription drugs without a physician's prescription, and 30% of the sample had at least one close friend who misused prescription drugs. Conclusions: Prescription drug misuse is prevalent in college students' social networks, and more so among those who themselves misuse prescription drugs, suggesting the need for prevention specialists to provide younger adults with information regarding the detrimental consequences of prescription drug misuse for themselves and their friends. Published by Elsevier Ltd.