Neonatal calf diarrhea (NCD) is the leading health concern in calves during the first weeks of their lives. In this narrative review, the potential for pathogen-oriented approaches for NCD is discussed. The literature on NCD clearly shows substantial differences in spread and characteristics between the major NCD pathogens, making pathogen-oriented approaches possible, justifying the use of etiological diagnostics. For enterotoxic Escherichia coli, colostrum delivery and dam vaccination, biosecurity around calving and antimicrobial therapy are key. Both for bovine coronavirus (BCV) and bovine rotavirus (BRV), biosecurity and disinfection, dam vaccination in combination with adequate and prolonged colostrum delivery are the essentials. However, a different focus concerning biosecurity is necessary given the airborne spread of BCV and higher environmental persistence of BRV. For an effective Cryptosporidium spp. control, the use of disinfectants that kill oocysts is crucial. Evidence supporting the prophylactic use of halofuginone lactate to reduce shedding and diarrhea, is available, but in terms of biosecurity, attention should be placed on the proper use of this product. In case of a Salmonella enterica outbreak, antimicrobial use remains important, and biosecurity wise, attention should be paid to shedding of periparturient cows in the calving pen and administration of infected colostrum. Both for S. enterica and cryptosporidiosis, farm staff should be informed on how to protect themselves against these zoonotic infections. Nutritional factors play an additional role within NCD. Improper nutrition management can induce diarrhea or can further enhance infectious NCD through osmosis or dysbiosis. In conclusion, the suggested pathogen-oriented approaches can aid to economize labor and financial investments, limit the environmental impact of NCD control and prevention and valorize tailor-made farm advisory work.