This paper provides an overview of the conceptualization and methods used in the National Survey of American Life (NSAL). The objectives of the NSAL are to investigate the nature, severity, and impairment of mental disorders among national samples of the black and non-Hispanic white (n = 1,006) populations in the US, including African American (N = 3,570), and Afro-Caribbean (N = 1,623) immigrant and second and older generation, populations. National multi-stage probability methods were used in generating the samples and race/ethnic matching of interviewers and respondents were employed in the largely face-to-face interview, lasting on average 2 hours and 20 minutes. Two methodological approaches are described for addressing sampling coverage of individuals attached to, but not residing in, selected households at the time of the study. The paper also describes two approaches used to address concerns about the interpretations of standard symptom probe information in assessing serious mental disorders. This included a clinical reappraisal study designed to ascertain differences in symptom responding and ascertainment of cases (N = 677) in a subset of the same NSAL respondents. Finally, an abbreviated, novel method for estimating the prevalence of mental disorders in first-degree family members is described and the preliminary results from this new approach are reported.