It has been suggested that a basal level of NOX2 activity is required for normal heart function and that suppression of NOX2 can induce cardiac injury (Zhang et al., 2013; Donoso et al., 2014), a concept encompassed in the title “NADPH oxidases in heart failure: poachers or gamekeepers?” (Zhang et al., 2013). The gene discussed is FMO5; the disease is heart failure.