Objective: To evaluate the feasibility and impact on clinical response and function associated with the use of an algorithm-driven disease management program (ALGO) for children and adolescents treated for depression with or without attention-deficit/hyperactivity disorder (ADHD) in community mental health centers. Method: Interventions included (1) medication algorithms, (2) clinical and technical support for the physician, (3) uniform chart documentation of outcomes, and (4) a patient/family psychoeducation program. Children eligible for entry into the study were referred to the child psychiatrist for initiation or change in medicine. Outcomes of treatment with the ALGO for up to 4 months are presented. Measures of change included clinical symptoms, functioning, and global improvement (Clinical Global Impression Scale). A historical chart cohort from the same clinics was used as a quasi-control. Results: Thirty-nine individuals (depression = 24; comorbid depression with ADHD = 15) were enrolled for treatment with ALGO. One hundred fourteen children were in the control cohort (74 depressed, 40 comorbid). For the ALGO groups, Children's Depression Rating Scale-Revised depression severity scores decreased from 48.2 to 32.5 and Child Adolescent Functioning Assessment Scale function scores improved from 70.3 to 40.9 (all p [less than or equal to] .0005). Clinical Global Impression Scale severity scores decreased from 5.7 to 3.7 in ALGO compared to only 5.8 to 4.8 in the control (p less than .003). Conclusions: There was clear improvement in clinical symptoms, functioning, and global response with ALGO treatment. The magnitude of the improvement was greater in children and adolescents treated with the ALGO program compared with a historical cohort. These data support the need for controlled studies in larger populations examining the effects of algorithm-driven disease management programs on the clinical outcomes of children with mental illness.