The 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) (Synflorix™) includes ten serotype-specific polysaccharides of Streptococcus pneumoniae, eight of which are conjugated individually to a nonlipidated cell-surface lipoprotein (protein D) of non-typeable H. influenzae and two of which are conjugated to nontoxic tetanus or diphtheria toxoid carrier proteins. This article provides an overview of the well-established immunogenicity of PHiD-CV, including functional immune responses and immunologic memory, as well as immune responses in preterm infants and HIV-infected children. It also includes a brief discussion of cross-protection against vaccine-related serotypes (6A and 19A) and focuses on labelling in the EU, where PHiD-CV is approved for active immunization against invasive disease, pneumonia, and acute otitis media (AOM) caused by S. pneumoniae in infants and young children up to 5 years of age. Evidence of the protective efficacy and effectiveness of PHiD-CV against pneumococcal diseases is available from several studies, including the randomized, double-blind trials COMPAS (Clinical Otitis Media and Pneumonia Study) and FinIP (Finnish Invasive Pneumococcal disease), as well as postmarketing studies from various countries. As would be expected, protection against pneumonia or AOM is substantially lower than that against invasive pneumococcal disease, as many micro-organisms other than pneumococcal vaccine serotypes can cause pneumonia and AOM, thereby limiting the overall protection of PHiD-CV against these diseases. PHiD-CV has a safety and reactogenicity profile similar to that of other pneumococcal conjugate vaccines.