The majority of individuals gamble during their lifetime; however only a subset of these individuals develops problematic gambling. Gray's Reinforcement Sensitivity Theory may be relevant to understanding gambling problems. Differences in sensitivity to punishments and rewards can influence an individual's behavior and may be pertinent to the development of gambling problems. This study examined the functional associations between sensitivity to punishment (SP), sensitivity to reward (SR), and gambling problems in a sample of 2254 college students. Zero-inflated negative binomial regression was used to predict gambling problems as well as the absence of gambling problems. Gambling problems were hypothesized to be positively associated with SR and inversely associated with SP. In addition, SP was hypothesized to moderate the association between SR and gambling problems, attenuating the strength of the association. As hypothesized, SR was positively associated with gambling problems. However, SP did not moderate the relationship between SR and gambling problems. SP did, however, moderate the relationship between SR and the likelihood of never experiencing gambling problems. The results demonstrate that individual differences in SP and SR are functionally associated with gambling problems.