E. coli bacteria isolated from localized and systemic disease processes in poultry are designated as Avian Pathogenic E. coli (APEC). The disease-inducing potential of these isolates has been explained by the occurrence of specific virulence factors. Despite the extensive literature on virulence factors for E. coli, unambiguous markers of virulence have not been identified yet. The relationship between serotyping and virulence is not straightforward either and raises the question whether E. coli infections in poultry should mainly be considered as opportunistic. Investigations into the occurrence of certain (combinations of) virulence factors in APEC isolates as virulence markers should fulfil the molecular version of Koch's postulates if the former question is to be answered.