This article is one of a series focusing on how the preoperative optimization process, if designed for underserved communities, can improve access to care and reduce disparities. In this article, we specifically focus on methods to improve optimization for patients with HIV and hepatitis C to facilitate their access to total joint arthroplasty. 1.2 million Americans are currently living with HIV (people living with HIV). African Americans and Hispanics account for the largest proportion of new HIV diagnoses and make up the highest proportion of people living with HIV. HIV-positive patients, many of them with complex comorbidities, are at a high risk for postoperative complications. Optimization of this vulnerable cohort involves a multidisciplinary strategy focusing on optimizing treatment modalities to reduce viral loads, leading to lower complication rates and a safer environment for the surgical team. The rates of hepatitis C have been increasing in the United States, and more than half of individuals living with hepatitis C are unaware that they are infected. Hepatitis C infections are highest in African Americans, and the rates of chronic hepatitis C are highest in those born outside the United States. Patients with hepatitis C have an increased risk for surgical complications after total joint arthroplasty, and studies have demonstrated that these risks normalize when patients are preoperatively screened and treated. Optimization in these vulnerable groups includes working closely with psychosocial resources, the primary care team, and infectious disease specialists to ensure treatment access and compliance.