Schizophrenia and human immunodeficiency virus (HIV) infection both are associated with high rates of neurocognitive impairment. These impairments predict unemployment in both disorders, independent of other disease-related factors that may affect employment. In this study, we investigated work-related abilities and previous employment patterns in 27 unemployed patients with schizophrenia, 27 demographically matched unemployed HIV-infected participants, and 27 nonmatched employed HIV seropositive (HIV+) participants. All subjects were administered a computerized and hands-on assessment of vocational abilities and a comprehensive work history interview. Compared with the employed HIV+ group, the two unemployed groups had lower estimates of maximal lifetime job functioning. In terms of current vocational abilities, the employed HIV+ subjects generally performed best, followed by the unemployed HIV+ subjects and the patients with schizophrenia. Although the unemployed schizophrenia subjects had the most decline in vocational abilities (from estimated lifetime maximum level), the patterns of decline were similar in the two unemployed groups and were suggestive of parallel impairments in frontal-subcortical functioning.