To control both fasting and prandial plasma glucose levels in people with diabetes, insulin therapy must mimic "normal" physiological insulin secretion as much as possible. This is achieved with a long-acting insulin injected once or twice daily and a bolus of insulin injected before every meal. Prandial (bolus) insulin can either be regular human insulin (RHI) or a rapid-acting insulin analogue (RAIA). Although the efficacy of RHI has been established over approximately 35 years of clinical use, RAIAs offer several clinical advantages over RHI, namely that they have been engineered with a reduced tendency to aggregate as hexamers, which allows for rapid dissociation and absorption after a subcutaneous injection. Conventional RAIAs include insulin lispro, insulin aspart, and insulin glulisine. The more recently developed fast-acting insulin aspart (faster aspart) is an ultrafast-acting mealtime insulin that contains the conventional insulin aspart in a new formulation with the excipients niacinamide and L-arginine to achieve faster insulin absorption than RHI and the conventional insulin aspart formulation. This article reviews the clinical evidence supporting the use of RAIAs as part of a basal-bolus regimen in patients with diabetes, with a focus on new formulations whose pharmacological profiles more closely mimic the endogenous prandial insulin secretion pattern that is seen in individuals without diabetes. This review also provides a clinical perspective to help guide health care professionals in the use of RAIAs.