After viral and bacterial pathogens enter the cell, they use host proteins to complete their life cycles. Recently, ACBD3 is shown to interact with many pathogen proteins and affect the replication of pathogens. This review will summarize the interplay between ACBD3 and different pathogens, including Aichi virus, Coxsackie virus, poliovirus, hepatitis C virus, human rhinovirus and Salmonella, and discuss the role of ACBD3 in pathogen replication.