Hypoglycemia is a common, potentially avoidable consequence of diabetes treatment and is a major barrier to initiating or intensifying antihyperglycemic therapy in efforts to achieve better glycemic control. Therapy regimen and a history of hypoglycemia are the most important predictors of future events. Other risk factors include renal insufficiency, older age, and history of hypoglycemia-associated autonomic failure. Reported rates of hypoglycemia vary considerably among studies because of differences in study design, definitions used, and population included, among other factors. Although occurring more frequently in type 1 diabetes, hypoglycemia also is clinically important in type 2 diabetes. Symptoms experienced by patients vary among individuals, and many events remain undiagnosed. The incidence of severe events is unevenly distributed, with only a small proportion (∼5%) of individuals accounting for >50% of events. Consequently, clinicians must be conscientious in obtaining thorough patient histories, because an accurate picture of the frequency and severity of hypoglycemic events is essential for optimal diabetes management. Severe hypoglycemia in particular is associated with an increased risk of mortality, impairments in cognitive function, and adverse effects on patients' quality of life. Economically, hypoglycemia burdens the healthcare system and adversely affects workplace productivity, particularly after a nocturnal event. Ongoing healthcare reform efforts will result in even more emphasis on reducing this side effect of diabetes treatment. Therefore, improving patients' self-management skills and selecting or modifying therapy to reduce the risk of hypoglycemia will increase in importance for clinicians and patients alike.