Bisexuals represent the largest sexual minority group, and they experience disproportionate mental and behavioral health risks compared to monosexuals. There is a dearth of psychotherapy and intervention research focused specifically on bisexuals, although evidence-based practice for this population can draw on professional expertise, qualitative and analog research, quantitative descriptive studies, and randomized controlled trials that include bisexual participants. This chapter reviews these literatures and offers guidance for practice and future directions for research. Informed and reflective practice is recommended to develop a strong working alliance, enhance case conceptualization and collaboration, and adapt manualized treatments. Validation, social support, and attention to bisexual-specific mental health stressors may be especially important, given the pervasiveness of binegativity, bisexual stereotypes, and invisibility of bisexuality. Evidence-based practice with this population will be strengthened by future research that specifically investigates bisexuality in mental health practice.