As influenza viruses continue to jump species barriers to cause human infection, assessments of disease severity and viral replication kinetics in vivo provide crucial information for public health professionals. The ferret model is a valuable resource for evaluating influenza virus pathogenicity; thus, understanding the most effective sample collection and usage techniques, as well as the full spectrum of attainable data following experimental inoculation in this species, is paramount. This is especially true for scheduled necropsy of virus-infected ferrets, a standard component in evaluation of influenza virus pathogenicity, as necropsy findings can provide important information regarding disease severity and pathogenicity that is not otherwise available from the live animal. In this review, we describe the range of influenza viruses assessed in ferrets, the measures of experimental disease severity in this model, and optimal sample collection during necropsy of virus-infected ferrets. Collectively, this information is critical for assessing systemic involvement following influenza virus infection in mammals.