Viral respiratory infections remain a significant cause of morbidity and mortality in pediatric, elderly, and immunocompromised patients. The Panther Fusion respiratory panels consist of 3 separate multiplex assays that test for 1) influenza A, influenza B, and RSV; 2) parainfluenza virus types 1-4; or 3) adenovirus, human metapneumovirus, and rhinovirus. This study evaluated the performance of the Fusion assays for both upper and lower respiratory tract specimens in comparison to routine methods, including viral culture and targeted real-time polymerase chain reaction assays. Following discordant resolution, the Fusion assays demonstrated high overall correlation (98.6% [648/657]) with routine methods. In addition, prospective testing of respiratory specimens (n = 146) submitted for viral culture showed a ~10-fold increase in detection by the Fusion panels compared to viral culture (28.1% versus 2.7% positivity). The Fusion respiratory panels offer a flexible, more targeted approach to respiratory virus testing with a turnaround time comparable to other molecular assays.