Social isolation is a major force in the lives of gay men and lesbians in the Great Plains, especially in small towns and rural areas. This isolation results from the region's great distances and low population density, the conformist and privacy-guarding aspects of rural and small-town life, and the tendency of many gays and lesbians to leave their hometowns for larger cities within and outside the region. In urban places it is generally easier for them to be themselves and to connect with other gays and lesbians.

Though the intensity of this migration has possibly lessened in recent years, it continues, and it helps to foster the idea among many heterosexuals that homosexuality is an exclusively urban phenomenon, irrelevant to rural or small-town life. Many gays and lesbians who stay in their small communities strengthen this belief by concealing their homosexuality, or by denying and suppressing it in order to follow a traditional life pattern that typically includes marriage and child rearing. Growing up in a homogeneous and conformist community, lacking information and openly gay role models, gay and lesbian youth are likely to perpetuate this pattern.

In recent years, with television and other vehicles of popular culture depicting gays and lesbians living openly, gay and lesbian youth are less likely to remain ignorant of, or confused by, their natures and are less susceptible to making life choices that are rooted in concealment and pretense. Internet access to supportive information and social connections is especially valuable to the most isolated gays and lesbians, perhaps reducing their likelihood of attempting suicide or engaging in substance abuse, unsafe sexual practices, or other self-destructive behaviors.

Great Plains culture celebrates individualism, but only within the tightly delimited boundaries of conventional gender identity. Females are allowed somewhat more latitude to stray from the feminine ideal than are males to deviate from the masculine. Especially when it is combined with fundamentalist interpretations of biblical texts and with the puritanism of Judeo-Christian culture, this gender-role rigidity is a powerful enforcer of the heterosexual norm.

No state or provincial government of the Plains region has been progressive in extending full civil rights to gay men and lesbians. In many places, their consensual sexual activity is criminalized, their access to housing and employment is threatened, and the recognition of marriage or domestic partnership for their committed relationships is denied. It is not uncommon for acts of antigay violence to be viewed with indifference or a sense of being deserved. In a widely publicized case, Matthew Shepard was murdered in Laramie, Wyoming, in 1998. Though he was a native of that state, the twenty-one-year-old had attended high school in Europe and had lived on the East Coast. Returning to Wyoming, he brought with him a manner of self-presentation that proved to be fatally at odds with Plains culture: he would not, or could not, conceal his gayness.

Before contact with Europeans, many Native cultures of the Plains accommodated and even valued gender-atypical males and females. Regarded as a blend of woman and man, these individuals were clearly counterparts of contemporary gays and lesbians, but their differences from typical men and women were understood by their tribes to be more complex than simply "sexual orientation." Seen as having special talents, they performed well-defined and respected functions within their communities: artists, healers, mediators, keepers of cultural traditions. As Native cultures have been eroded or destroyed, so have these intermediate gender identities, though some contemporary Native Americans are embracing and reviving them–preferring to call themselves two-spirit rather than gay or lesbian.