Abl nonreceptor tyrosine kinases are activated by multiple stimuli and regulate cytoskeletal reorganization, cell proliferation, survival, and stress responses. Several downstream pathways have direct impact on physiological processes, including development and maintenance of the nervous and immune systems and epithelial morphogenesis. Recent studies also indicated that numerous viral and bacterial pathogens highjack Abl signaling for different purposes. Abl kinases are activated to reorganize the host actin cytoskeleton and promote the direct tyrosine phosphorylation of viral surface proteins and injected bacterial type-III and type-IV effector molecules. However, Abl kinases also play other roles in infectious processes of bacteria, viruses, and prions. These activities have crucial impact on microbial invasion and release from host cells, actin-based motility, pedestal formation, as well as cell-cell dissociation involved in epithelial barrier disruption and other responses. Thus, Abl kinases exhibit important functions in pathological signaling during microbial infections. Here, we discuss the different signaling pathways activated by pathogens and highlight possible therapeutic intervention strategies.