Transgender and gender nonbinary people comprise a vulnerable population due to discrimination they face in society in general as well as in healthcare settings. Internal medicine physicians can be equipped to provide patient-centered, sensitive, and evidence-based care for transgender patients. In this chapter, I review the role of the internist in providing gender-affirming primary care, including approach to the initial assessment, hormone therapy regimens and effects, and special considerations. I encourage readers who are interested in providing gender-affirming care in their clinical practice to familiarize themselves with the guidelines and resources in this field.