The healthy worker effect (HWE), which can mask mortality excesses resulting from occupational exposures, poses a methodological problem for those who study occupational cohorts. This problem is further complicated by the fact that the strength of the HWE may vary from one occupational cohort to another. Understanding the HWE is particularly important for investigators of nuclear worker cohorts, because screening associated with the security clearance process may amplify the HWE among certain subpopulations of nuclear workers. This review suggests that the HWE is modified by a number of factors, including gender, race, age at hire, occupational class, length of employment, monitored status, length of follow-up, and cause of death. In general, these factors operate similarly in nuclear and other occupational cohorts. Given that many of these factors may be highly correlated with exposure, or proxy measurements for exposure, it is important for investigators to understand how these factors relate independently with mortality. Continuing to document the HWE and its changes over time is essential to the proper interpretation of exposure effects in occupational cohorts in general, and in nuclear cohorts in particular.