Sulphonylureas (SUs) and biguanides (metformin) are the current mainstays in the treatment of type 2 diabetes (T2DM) and represent the most commonly used oral hypoglycaemic agents (OHAs). In recent years, a variety of new OHAs have become available, including thiazolidinediones, glinides, alpha-glucosidase inhibitors, glucagon-like peptide-1 agonists, amylin analogues and dipeptidyl peptidase-IV inhibitors, providing physicians with a larger therapeutic catalogue than ever before. The traditional drugs metformin and SUs have an established safety profile through long-term use. However, long-term clinical trials and routine use are lacking for many of the new agents, and some potentially serious side effects have been reported with several of these compounds. Until adequate data is obtained, it is difficult to assess the risk-benefit ratio of these agents in relation to the traditional drugs. Until that becomes fully documented, it may be wise to start pharmacologic treatment of patients on an individual basis, weighing the benefits and costs of each medication. Thus, there remains a place for well-established drugs that have a proven safety record and are supported by years of clinical use for the treatment of T2DM.