Beliefs about medication are associated with treatment adherence and outcome. This is a secondary analysis of the role of beliefs and attitudes about bupropion in treatment adherence and smoking cessation outcomes using data from a smoking cessation trial of open-label sustained-release (SR) bupropion therapy reported previously (Toll et al., 2007). Positive beliefs and attitudes were positively correlated with intentions, desire, confidence, and motivation to quit smoking; expectation of quitting success; perceived benefits of quitting; and perceived disadvantages of smoking. Positive beliefs were also associated with greater medication adherence, an increased likelihood of completing treatment and being continuously abstinent, and a delayed latency to smoking lapse. These findings provide preliminary support that positive beliefs and attitudes about bupropion are associated with positive attitudes toward quitting, better treatment adherence, and potentially better treatment response.