Diabetes mellitus diagnosed during the first 2 years of life differs from the disease in older children regarding its causes, clinical characteristics, treatment options and needs in terms of education and psychosocial support. Over the past decade, new genetic causes of neonatal diabetes mellitus have been elucidated, including monogenic β-cell defects and chromosome 6q24 abnormalities. In patients with KCNJ11 or ABCC8 mutations and diabetes mellitus, oral sulfonylurea offers an easy and effective treatment option. Type 1 diabetes mellitus in infants is characterized by a more rapid disease onset, poorer residual β-cell function and lower rate of partial remission than in older children. Insulin therapy in infants with type 1 diabetes mellitus or other monogenic causes of diabetes mellitus is a challenge, and novel data highlight the value of continuous subcutaneous insulin infusion in this very young patient population. Infants are entirely dependent on caregivers for insulin therapy, nutrition and glucose monitoring, which emphasizes the need for appropriate education and psychosocial support of parents. To achieve optimal long-term metabolic control with low rates of acute and chronic complications, continuous and structured diabetes care should be provided by a multidisciplinary health-care team.