In the last few years, transgender and gender nonconforming people have become more visible in our society, which has sparked a marked increase in awareness, interest, and attention among psychologists. Questions have emerged about the extent to which psychologists are able to work competently with this population. This article presents a framework for understanding key clinical issues that psychologists who work with transgender and gender nonconforming individuals will likely encounter in their clinical work. This article does not address the knowledge and skills required to provide services related to gender transition, but rather to provide other psychological services that these clients may need, in light of the high levels of gender-related victimization and discrimination to which they are exposed. An adaptation of the Minority Stress Model (Meyer, 2003) is presented and translated to incorporate the unique experiences encountered by transgender and gender nonconforming individuals. In particular, we examine adverse experiences that are closely related to gender identity and expression, resulting expectations for future victimization or rejection, and internalized transphobia. The impact of Minority Stress Model factors on suicide attempts is presented as a detailed example. Mechanisms by which transgender and gender nonconforming persons develop resilience to the negative psychological effects of these adverse experiences are also discussed. Recommendations for clinicians are then made to assist psychologists in developing competence in working with this population.