In a recent article in ASM Case Reports, G. P. Higerd-Rusli, A. Karan, S. A. Hoffman, I. E. A. Morante, et al. (ASM Case Rep 2:e00165-25, 2025, https://doi.org/10.1128/asmcr.00165-25) describe one confirmed and one probable case of influenza A(H5N1) detected through universal subtyping of influenza A-positive specimens, including cases without known animal exposure. These findings highlight the limitations of exposure-based testing strategies and raise important questions about early detection of emerging pathogens. Drawing on lessons from prior pandemics, this commentary examines the tradeoffs between targeted and expanded surveillance and emphasizes the need for adaptive, flexible approaches to laboratory preparedness.