Concerns about potential sex and gender bias during impairment and disability evaluations have been raised; this article reviews ways in which sex and gender contribute to the unique presentation, manifestations, treatment, and functional outcome of medical conditions and how these differences can be appropriately addressed using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Sixth Edition. Sex differences are objective and are based on biochemical and biological factors; gender refers to cultural attitudes that are learned and vary by culture, history, and ethnicity. The AMA Guides acknowledges individual variations and advocates a flexible approach: Physicians can choose among sections of the AMA Guides those best suited to account for individual and sex differences. The AMA Guides does not advocate different evaluation of medical conditions based on sex, except for sex-specific disorders (eg, unique male or female reproductive organs). The health care system is striving to eliminate gender and sex bias, and impairment and disability are following by attempting to eliminate bias by offering individualized assessments of how impairment affects the injured organ, use of unique rating methods to fully characterize the impairment, use of rating ranges to account for individual variability and sex, and by ascribing equal values to gender-ascribed activities of daily living.