HIV infection affects all aspects of a person’s occupational functioning. This article examines the application of the Model of Human Occupation (Kielhofner & Burke, 1980) to adults with HIV. An occupational therapy assessment battery based on the model is introduced. Given the physical, psychosocial, and environmental needs of persons with HIV, the assessment must be comprehensive to fully evaluate the effect of HIV on occupational behaviors. Goal planning and treatment follow the assessment process. A case example illustrates the integration of the Model of Human Occupation with clinical practice.