Background: Findings are inconsistent regarding the degree to which depression may exert a negative impact on glycemic control in patients with type 2 diabetes. We therefore aimed to examine the longitudinal relationship between depression, behavioral factors, and glycemic control. Methods: In a prospective component of a nationally representative sample, 866 patients with type 2 diabetes aged ≧18 years completed a standardized assessment including a laboratory screening, questionnaires, and diagnostic measures. Subsequent to baseline (t0), patients were tracked over a period of 12 months (t1). Depression was assessed according to DSM-IV and ICD-10 criteria. Glycemic control was determined by levels of glycosylated hemoglobin (HbA1c); a level of ≧7% was judged as unsatisfactory. Regression analyses were performed to analyze the prospective relationship between depression, medication adherence, diabetes-related health behavior, and HbA1c. Results: Patients with depression at t0 revealed increased rates of medication nonadherence (adjusted OR: 2.67; CI: 1.38–5.15) at t1. Depression (adjusted regression coefficient: β = 0.96; p = 0.001) and subthreshold depression (β = 1.01; p < 0.001) at t0 also predicted increased problems with diabetes-related health behavior at t1. Adjusted ORs for poor glycemic control (HbA1c ≧7%) at t1 were also increased for patients with baseline depression (2.01; CI: 1.10–3.69). However, problems with medication adherence as well as problems with diabetes-related health behavior at t0 did not predict poor glycemic control at t1. Conclusions: In a prospective representative study of patients with type 2 diabetes, baseline depression predicted problems with medication adherence, problems with health-related behaviors, and unsatisfactory glycemic control at follow-up.