The dipeptidyl peptidase (DPP)-4 inhibitors are a new class of antihyperglycaemic agents which were developed for the treatment of type 2 diabetes by rational drug design, based on an understanding of the underlying mechanism of action and knowledge of the structure of the target enzyme. Although they differ in terms of their chemistry, they are all small molecules which are orally available. There are some differences between them in terms of their absorption, distribution, metabolism and elimination, as well as in their potency and duration of action, but their efficacy, both in terms of inhibiting plasma DPP-4 activity and as antidiabetic agents, appears to be similar. They improve glycaemic control, reducing both fasting and postprandial glucose levels to lower HbA1c levels, without weight gain and with an apparently benign adverse event profile. At present, there seems to be little to distinguish between the different inhibitors in terms of their efficacy as antidiabetic agents and their safety. Long-term accumulated clinical experience will reveal whether compound-related characteristics lead to any clinically relevant differences.