Gender is a complex bio-psycho-social component of the psyche, and variability in the experience of gender exists as with all other complex bio-psycho-social phenomena. Many individuals experience life with a gender that does not align with the sex assigned at birth, called Gender Incongruence or Gender Dysphoria. This phenomenon has existed throughout human history, with variable levels of acceptance of individuals who experience gender incongruence. In this chapter, we will discuss the normal development of a gendered sense of self and recommendations for polite, ethical interactions with persons experiencing gender incongruence.