Antivirals form a foundation for protecting immunocompromised individuals (ICIs) from influenza complications. Neuraminidase inhibitors have demonstrated benefit for both prophylaxis and treatment in ICIs, including when given >48?hours after symptom onset. Baloxavir is a newer antiviral that has potent effects on viral kinetics in immunocompetent people, but data on baloxavir in ICIs are currently limited. Optimization of antiviral therapy to minimize viral replication within ICIs and reduce the risk of treatment-emergent antiviral resistance (eg, through combination regimens) may prevent viral evolution within ICIs and mitigate transmission of virulent or resistant variants to the general public. Unfortunately, ICIs have been excluded from most clinical trials evaluating novel influenza preventive and therapeutic strategies. Inclusion of ICIs in such clinical trials is essential to facilitate acquisition of clinical and virologic data in patients with specific immunocompromising conditions and ensure that ICIs have equitable access to valuable interventions.