Sexual development is a complex but vital part of the human experience. People with significant disabilities are not excluded from this principle, but often may be prevented from receiving high-quality and comprehensive instruction necessary for a healthy sexual life. The functional model of self-determination emphasizes increasing knowledge, access to environments, and positive self-perceptions and may be an effective framework for the delivery of sexuality education to people with significant disabilities. We explored ways in which self-determination and sexuality education for people with significant disabilities are aligned. We also conducted a systematic review of sexuality education intervention research for this population and found significant gaps related to self-determined sexuality. Suggestions for sexuality education for persons with significant disabilities as well as barriers are presented and implications for stakeholders and future researchers are discussed.