Guided by a culturally informed illness representation self-regulation model (CIRSRM), this study analyzed the relations among 223 Asian Americans' lay beliefs about depression, enculturation to Asian values, and their likelihood of seeking professional help for depression. Participants' lay beliefs were assessed through an analysis of written responses to open-ended questions about depression. Enculturation as well as beliefs in biological causes, situational causes, and a short duration of depression were significantly related to the likelihood of professional help seeking. In addition, enculturation moderated the association between several lay beliefs and the endorsement of professional help seeking. The findings are discussed in light of how clinicians can incorporate mental illness lay beliefs in their work with Asian Americans. © 2010 Wiley Periodicals, Inc. J Clin Psychol 66: 317–332, 2010.