ABSTRACTAnimal studies suggest that the gut‐brain peptide ghrelin plays an important role in the neurobiology of alcohol dependence (AD). Human studies show an effect of alcohol on ghrelin levels and a correlation between ghrelin levels and alcohol craving in alcoholics.This investigation consisted of two studies. Study 1 was a 12‐week study with alcohol‐dependent subjects, where plasma ghrelin determinations were assessed four times (T0‐T3) and related to alcohol intake and craving [Penn Alcohol Craving Score (PACS) and Obsessive Compulsive Drinking Scale (OCDS)]. Serum growth hormone levels and assessment of the nutritional/metabolic status were also performed. Study 2 was a pilot case‐control study to assess ghrelin gene polymorphisms (Arg51Gln and Leu72Met) in alcohol‐dependent individuals. Study 1 showed no significant differences in ghrelin levels in the whole sample, while there was a statistical difference for ghrelin between non‐abstinent and abstinent subjects. Baseline ghrelin levels were significantly and positively correlated with the PACS score at T1 and with all craving scores both at T2 and T3 (PACS, OCDS, obsessive and compulsive OCDS subscores). In Study 2, although there was a higher frequency of the Leu72Met ghrelin gene polymorphism in alcohol‐dependent individuals, the distribution between healthy controls and alcohol dependent individuals was not statistically significant.This investigation suggests that ghrelin is potentially able to affect alcohol‐seeking behaviors, such as alcohol drinking and craving, representing a new potential neuropharmacological target for AD.