The authors studied 126 elderly patients without dementia and with unipolar major depression. Impairment in instrumental activities of daily living (IADLs) was significantly associated with age (P<0.0001), gender (P<0.001), medical burden (P=0.013), severity of depression (P=0.01), initiation/perseveration (IP; P=0.035), and IP x depression (P=0.029). Depression was associated with IADL impairment mainly in patients with impaired IP. Among the cognitive impairments, IP-only contributed significantly to IADL impairment, whereas attention, construction, conceptualization, and memory did not. Attention to executive function and disability may guide clinical management and lead to development of innovative pharmacological and behavioral interventions.