In clinical practice with the transgender and gender non-conforming population, a historically marginalized and mistreated population, it is vital for clinicians to practice from a place of awareness, education, and cultural humility. This presentation provides a strong foundation of knowledge for educated clinical interactions, including basic terminology, information about the disparities faced by this population, and guidance for engaging in sensitive clinical practice with cultural humility, including at end-of-life, and establishing safer environments, both in healthcare settings and when care providers are in the home.