Glucose-dependent insulinotropic polypeptide (GIP) is a gut hormone impacting glucose, lipid and bone metabolism through the GIP receptor (GIPR). The GIP system has key species differences complicating the translation of findings from rodent to human physiology. Furthermore, the effects of endogenous GIP in humans have been difficult to tease out due to the lack of a suitable GIPR antagonist. The naturally occurring GIP(3-30)NH₂ has turned out to constitute a safe and efficacious GIPR antagonist for rodent and human use. To study GIP physiology, it is recommended to use the species-specific GIP(3-30)NH₂ peptide sequence, and for human intravenous infusions, an antagonist:agonist ratio of a minimum of 600 with a 20 min infusion time before the intervention of interest is recommended. Several studies using GIP(3-30)NH₂ are coming, hopefully providing new insights into the physiology of GIP, the pathophysiologic involvement of GIP in several diseases and the therapeutic potential of the GIPR.