Background: Late-life depression is a heterogeneous disorder, whereby cognitive impairments are often observed. This study examines which clinical characteristics and symptom dimensions of late-life depression are especially impacting on specific cognitive domains. Methods: Cross-sectional data of 378 depressed and 132 non-depressed older adults between 60-93 years, from the Netherlands Study of Depression in Older adults (NESDO) were used. Depressed older adults were recruited from both inpatient and outpatient mental healthcare institutes and general practices, and diagnosed according to DSM-IV-TR criteria. Multivariable associations were examined with depression characteristics (severity, onset, comorbidity, psychotropic medication) and symptom dimensions as independent variables and cognitive domains (episodic memory, processing speed, interference control, working memory) as dependent variables. Results: Late-life depression was associated with poorer cognitive functioning. Within depressed participants, higher severity of psychopathology and having a first depressive episode was associated with poorer cognitive functioning. The use of tricyclic antidepressants, serotonergic and noradrenergic working antidepressants, and benzodiazepines was associated with worse cognitive functioning. Higher scores on the mood dimension were associated with poorer working memory and processing speed, whereas higher scores on a motivational and apathy dimension were associated with poorer episodic memory and processing speed. Conclusions: Heterogeneity in late-life depression may lead to differences in cognitive functioning. Higher severity and having a first depressive episode was associated with worse cognitive performance. Additionally, different domains of cognitive functioning were associated with specific symptom dimensions. Our findings on the use of psychotropic medication suggest that close monitoring on cognitive side effects is needed. Copyright © International Psychogeriatric Association 2014.