Clinical interventions for extramarital involvement (EMI) have outpaced empirical knowledge about both risk factors for infidelity and effective treatments. Allen et al. (this issue) provide a systematic review of current knowledge organized around stages of the development of EMI and factors concerning the involved partner, the spouse, the couple's relationship, and the interpersonal context. Their review identifies significant gaps in knowledge for which research is needed. Because EMI has multiple determinants, conceptual models and research on it must be multivariate. This comment focuses on priorities for increasing knowledge about EMI, including (a) clarification of variation in definitions and personal standards for EMI through consideration of participants’ subjective experiences as well as the views of outsiders (researchers, clinicians); (b) improved qualitative research using interview methods designed to minimize biased questioning by investigators and biased reporting by subjects, to tap individuals’ internal experiences with the developmental process of EMI; (c) nonblaming research on characteristics of the noninvolved spouse and the couple's interaction that predict EMI; and (d) adaptation of generic preventive and relationship enrichment interventions for couples involving communication skill-building and psychoeducation, to include information about ways to “inoculate” relationships against commonly unexpected risks of EMI.