Alcohol dependence is associated with genetic variants of alcohol-metabolizing enzymes and genes related to dopaminergic, gamma-aminobutyric acidergic, glutamatergic, opioid, cholinergic, and serotonergic systems. Genetic variations in the endogenous cannabinoid system are also involved in alcohol dependence. The present study aimed to evaluate the association between three polymorphisms, DRD2 TaqIA, 5-HT1B A-161T, and CNR1 1359 G/A (rs1049353), and alcohol dependence. One hundred twenty three patients who were admitted to the Alcohol and Substance Abuse Center of Denizli State Hospital and diagnosed with alcohol dependence according to the DSM-IV criteria and 125 healthy volunteers were included in the study. Of the three polymorphisms investigated, 5-HT1B A-161T was the only one found to be associated with alcohol dependence. The 5-HT1B receptor A-161T polymorphism might be a promising marker for alcohol dependence; however, future studies are needed to clarify these findings.