About 20,550 larvae, pupae and adults of the codling moth, Cydia pomonella L., were diagnosed for pathogens during long-term investigations (1955–2012) at the Institute for Biological Control in Darmstadt, Germany. The prevailing entomopathogens diagnosed in these studies were insect pathogenic fungi, especially Beauveria bassiana and Isaria farinosa, the microsporidium, Nosema carpocapsae, the Cydia pomonella granulovirus (CpGV), as well as mostly undetermined bacteria. While the CpGV was observed exclusively in larvae and pupae from laboratory colonies or from field experiments with this virus, entomopathogenic fungi were most frequently diagnosed in last instars in autumn and in diapausing larvae and pupae in spring. B. bassiana was identified as the major fungal pathogen, causing larval prevalences of 0.9% to 100% (mean, about 32%). During prognostic long-term studies in larvae and adults of C. pomonella, N. carpocapsae was diagnosed in codling moth populations from various locations in Germany. The mean prevalence generally ranged between 20% and 50%. Experiments revealed that the fecundity and fertility of microsporidia-infected female adults were significantly reduced compared to healthy ones. The results underpin the importance of naturally occurring microbial antagonists and represent a base for further ecological studies on developing new or additional biological and integrated control strategies.