Chronic and aggressive periodontal diseases are characterized by the failure to resolve local inflammation against periodontopathogenic bacteria in the subgingival biofilm. Alveolar bone resorption is associated with altered innate and adaptive immune responses to periodontal pathogens. Macrophage-derived cytokines, chemokines and growth factors, present in both destructive and reparative phases of periodontitis, are elevated in numerous animal and human studies. Macrophage polarization to either a predominantly pro-inflammatory or anti-inflammatory phenotype may be a critical target for monitoring disease activity, modulating immune responses to subgingival biofilms in patients at risk and reducing alveolar bone loss.