This chapter describes the problem of LGBTQI2 (lesbian, gay, bisexual, transgender, questioning, intersex or two-spirit) along with its assessment; diagnosis; levels of prevention/intervention; primary, secondary, and tertiary strategies for dealing with the behavior; and additional resources. Sexual orientation, usually identified as heterosexual, homosexual, or bisexual, includes components of identity, attraction, and behavior in a person’s emotional, sexual, and/or relational attraction to others. Gender identity is a person’s sense of being male, female, or something else, whereas gender expression is how a person expresses his or her gender identity. Gender nonconforming youth are those whose gender expression differs from how their family, culture, or society expects them to act, behave, and dress. Stigmatization creates many issues for LGBTQI2 youth, including homelessness, altered body image, social anxiety, depression, suicidality, substance abuse, posttraumatic stress disorder, and other mental health issues.