There is an increasing focus on influenza in low-resourced areas as a vaccine-preventable cause of severe lower respiratory disease in young children, especially among those under two years of age. The extent of the disease burden is unclear: current etiologic studies may underestimate the impact of influenza if recognized or unrecognized infection occurs some time before severe disease manifestations prompt specimen collection for diagnosis. Because of various methodological challenges, a vaccine probe approach was used to estimate vaccine preventable disease incidence (VPDI) for Streptococcus pneumoniae and Haemophilus influenzae type b, particularly for pneumonia outcomes among young children. A similar approach could be used to determine VPDI for influenza. A highly effective vaccine would facilitate this approach; however, with appropriate design, a less than ideal vaccine also could be used to estimate VPDI. Because influenza vaccine efficacy against severe disease may be greater than against all symptomatic influenza disease, a vaccine probe approach could provide a better measure than etiologic studies of the public health utility of influenza vaccine. The first 6 months of life is a time of particularly increased influenza risk among young children, and an age group for which current vaccines are not approved. Previous studies have found that maternal influenza immunization can reduce acute respiratory infection in the infant during this vulnerable period. Additional randomized, controlled trials are currently underway using a vaccine probe approach to estimate VPDI among mothers and their infants following maternal influenza immunization. The World Health Organization now identifies pregnant women as the highest priority target group for influenza vaccination. Should countries implement this strategy, infants age 6–23 months likely would remain at increased risk; vaccine probe approaches could quantify the public health benefit of immunizing this group.