Despite a level “A” recommendation by the Centers for Disease Control and Prevention, the use of pneumococcal polysaccharide vaccination in patients with COPD is supported by limited data. Clinical and laboratory studies have suggested that the currently approved vaccine is less effective in the population of COPD patients than in healthier patients, and to date no randomized-controlled trial of pneumococcal vaccination for COPD patients has demonstrated any beneficial effect. The implementation of a pneumococcal vaccine trial in the COPD population is problematic because of the large sample size required for studies examining clinical outcomes and the fact that no adequate in vitro assays have been available to serve as surrogate measures of vaccine protection. However, new laboratory methods have been developed and more accurate determination of the immunogenicity of pneumococcal vaccines is now possible. There is considerable interest in the development of an improved pneumococcal vaccine for patients with COPD, and advances in vaccine design hold considerable promise for improved prevention against pneumonia and acute exacerbations caused by Streptococcus pneumoniae. The following discussion will examine the available data supporting pneumococcal polysaccharide vaccine use, the currently available laboratory methods to measure immunogenicity, and advances in the development of an improved pneumococcal vaccine that could better protect patients with COPD against this pathogen.