Preoperative optimization of a patient’s comorbidities is essential in reducing the risk of complications following revision total hip arthroplasty (rTHA). Although not all risk factors are modifiable, certain ones are. Cardiac disease, tobacco use, anemia, diabetes, obesity, alcohol and substance use, malnutrition, human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection, poor dentition, mental health, and social needs are associated with inferior THA outcomes and optimization of these risk factors decreases complications. The risk factors that may be modified depend upon whether the rTHA takes place in the subacute or acute setting. In the subacute setting, there is increased time for medical optimization prior to the need for surgery, allowing for optimization of more risk factors, particularly medical comorbidities. In the acute setting, revision surgery cannot wait for risk factor optimization therefore rapid recovery protocols (RRP) should be implemented, particularly hydration and carbohydrate loading, chlorhexidine decontamination, and Staphylococcus aureus decolonization. In all settings, medication reconciliation should be performed, and active medications must be adjusted or held prior to surgery, particularly glucocorticoids, methotrexate, cyclosporine, aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), and anticoagulation regimens. Ultimately, each rTHA scenario and patient comorbidity profile is unique and requires a patient-centered multidisciplinary effort in order to achieve the best possible outcome.