Objective: Increased numbers of transgender and gender-nonconforming people are presenting to physicians in the United States and abroad due to increased public recognition and acceptance and increased access to healthcare facilities. However, there are still gaps in medical knowledge among endocrinologists and other health care professionals. The purpose of these cases is to present several common clinical vignettes of transgender people presenting in an office setting that illustrate some of the key recommendations of the Endocrine Society's revised Endocrine Treatment of Gender Dysphoria/Gender Incongruent Persons guidelines, cosponsored by the American Association of Clinical Endocrinologists. Methods: Cases were developed based on these recently revised guidelines for gender-dysphoric and gender-nonconforming persons. Results: Six cases are presented that illustrate the diagnosis, treatment, and long-term management of trans-gender children and adults based on the revised guidelines for the endocrine care of gender-dysphoric and gender-nonconforming persons. Several key teaching points are presented from the presentation of these cases. Conclusion: Endocrinologists should be familiar with the revised guidelines for gender-dysphoric and gender-nonconforming persons. Important aspects of care are the diagnosis of gender dysphoria, the timing of treatment with gender-affirming hormones, and the long-term monitoring for potential adverse outcomes. Long-term health outcome studies are needed to further help guide care in this unique population. Abbreviations: BMI = body mass index GnRH = gonadotropin-releasing hormone HDL = high-density lipoprotein LDL = low-density lipoprotein.