Owing to its decades of use among patients of all ages and health conditions, oseltamivir has the most widely described pharmacokinetics (PK) and pharmacodynamics (PD) of all the modern influenza antivirals. Despite this, there remain numerous questions regarding optimal PK/PD parameters for oseltamivir and other neuraminidase inhibitors in populations at the highest risk for influenza-related complications including infants, young children, pregnant people, immunocompromised individuals, and those with altered clearance and drug distribution from critical illness, extracorporeal membrane oxygenation, and renal replacement therapies. Even less is known regarding the PK/PD of baloxavir—the first widely available cap-dependent endonuclease inhibitor—and the role that baloxavir may have alone and in combination with neuraminidase inhibitors for treating influenza in these populations. Support for further influenza antiviral PK and PD studies is needed to diversify and bolster our arsenal so that we may better protect and treat our most vulnerable patients.