Teleost immune responses towards bacterial infections follow initially a general pattern of reactions, including pathogen recognition, signal transduction, initiation of inflammatory reactions, production and release of innate effector molecules and subsequent establishment of adaptive responses with the involvement of T and B cells. Detailed descriptions of these factors and their regulation, biological function and genetic background are treated in various chapters of this book. However, a wide range of variations exist over this theme. The highly varying surface structure of the different bacterial types, encountered by fish, affects the outcome of the reactions—at both the early and late phases of infection. The fish host surface plays a role for pathogen attraction, adhesion and possible invasion of the host. Gram-negative fish bacteria such as Vibrio anguillarum, Aeromonas salmonicida, Yersinia ruckeri, Edwardsiella ictaluri, E. tarda, Flavobacterium psychrophilum, F. columnaris and F. branchiophilum elicit a different response compared to Gram-positive bacteria such as Renibacterium salmoninarum, Lactococcus garvieae, Streptococcus agalactiae, S. iniae, Mycobacterium marinum and M. fortuitum. The surface structures account for many of the pathogen-associated molecular patterns (PAMPs) interacting with the pattern recognition receptors (PRRs) in the host. In addition, the immune evasion strategies applied by the major bacterial groups explain the subsequent differences in host reaction patterns. The first infection phase involves PRRs such as TLRs and a fast expression of genes encoding AMPs together with SAA and other acute-phase reactants (precerebellin, hepcidin, lysozyme). The high upregulation of inflammatory cytokine genes (e.g. IL-1β, IL-8, TNF-α) is associated with a fast recruitment of leucocytes to the focus of infection. Different types of granulocytes, including neutrophils, possessing well-documented killing capabilities, are believed to explain a part of the initial elimination of pathogens. An array of acute-phase reactants (hepcidin, precerebellin, complement factors, CRP, MBL) represent some of the innate effector molecules. Production of antimicrobial peptides and reactive O and N species by leucocytes present in the affected tissue play a major role in the immediate killing of the invaders. Antigen-presenting cells (resident or systemic) at peripheral or central immune locations with aggregations of lymphocyte centres engulf and degrade the bacterial pathogen and present antigens with their MHC molecules to T cells carrying TCR whereafter B cells are stimulated to produce specific antibodies. Important factors influencing the response are the ontogenetic changes seen during the process from hatched yolk-sac larva via fry to the fingerling stage where the adaptive elements become increasingly dominating. Granuloma formation occurs when bacterial killing mechanisms are insufficient and sequestration of the pathogens may limit spread of the bacteria, which emphasizes the limitations of the piscine immune system. It has the capacity to recognize pathogens, activate both innate and adaptive components and eventually eliminate the invader. This is the basis for the successful application of a range of antibacterial vaccines in fish farming. Thus, the adaptive immune response of fish involves immunological memory securing reaction for an extended period, but the immune evasion strategies of the different bacterial types determine the type of reaction, the fate of the bacteria and the extent of protection.