Given the high prevalence of chronic obstructive pulmonary disease (COPD), the impact of exacerbations on quality of life, and the costs incurred, effective ways for the prevention of exacerbations, and for reductions in the severity and duration of COPD symptoms are needed. Bacterial immunostimulation has been advocated as a management strategy in COPD for the purposes of preventing acute exacerbations. In particular, it suggests that the use of oral multicomponent vaccines may reduce the severity and duration of acute episodes. The way in which bacterial extracts may exert their effects is not fully understood although a number of possible specific mechanisms have been suggested. Given the high prevalence of COPD worldwide and the high cost of acute exacerbations, some cost-effectiveness analyses suggest that bacterial immunostimulants may become a key element in the improved control of this condition. Nonetheless, larger and longer clinical trials are needed to investigate efficacy before oral vaccination could be recommended as part of the routine clinical management of COPD, mainly in advanced COPD. It remains also to be investigated whether this protective effect may be additive to the other treatments. In any case, it is well known that for Streptococcus pneumoniae, non-typable Haemophilus influenzae and Moraxella catarrhalis, recurrent infections occur because of strain heterogeneity. Therefore, a single or even multiple strain vaccine with a killed whole cell formulation is possibly not the ideal vaccine. Moreover, the method of inactivation can affect the immunogenicity of essential antigens through denaturation. For this reason, the efficacy of bacterial immunostimulants should not only be assessed but also compared.