This entry focuses on the pharmacokinetic (PK) challenges and therapeutic strategies for managing COVID-19 in disabled populations, who have been disproportionately affected by the pandemic. Disabled individuals often face unique PK complexities due to physiological and functional variations, such as altered drug absorption, metabolism, distribution, and excretion. These challenges are compounded by comorbidities, polypharmacy, and systemic inequities, necessitating tailored pharmacological approaches to optimize therapeutic outcomes. Renal and hepatic impairments, commonly observed among disabled individuals, significantly impact the clearance of critical COVID-19 therapeutics, such as remdesivir, increasing the risk of toxicity. Similarly, gastrointestinal abnormalities and changes in body composition affect drug bioavailability and distribution, requiring careful dose adjustments. The heightened risk of adverse drug reactions and drug–drug interactions further complicates treatment, particularly in the context of polypharmacy. This entry emphasizes the importance of individualized pharmacological interventions, including regular medication reviews and pharmacogenomic profiling, to address these challenges. Medication reviews can identify potential drug interactions, optimize polypharmacy management, and ensure the appropriateness of prescribed treatments. Pharmacogenomic profiling enables precise dosing based on genetic variations affecting drug metabolism, especially for medications reliant on cytochrome P450 enzymes. Clinicians are encouraged to adopt patient-centered approaches, emphasizing collaboration, accessible care plans, and caregiver involvement. Simplified medication regimens and tailored administration strategies are critical for improving adherence in individuals with cognitive or physical limitations. To reduce systemic disparities, inclusive research efforts, and the integration of disabled populations into clinical trials are essential. These strategies will refine therapeutic guidelines, improve health outcomes, and minimize inequities for disabled individuals during and beyond the COVID-19 pandemic.