Recent studies have afforded abundant evidences showing that Propionibacterium acnes (P. acnes) is involved not only in acne vulgaris, but also in many diseases, including endocarditis, endophthalmitis, osteomyelitis, joint, nervous system, cranial neurosurgery infections, and implanted biomaterial contamination. In spite of a range of P. acnes pathogenicity, its vaccine therapies have been studied much less intensively than antibiotic therapies which have been mainstay of treatment for P. acnes-associated diseases. Therefore, we have recently developed effective vaccines for P. acnes-associated inflammatory acne, consisting of a cell wall-anchored sialidase of P. acnes or killed-whole organism of P. acnes. Our data strongly show that immunization of ICR mice with the vaccines provides in vivo protective immunity against P. acnes challenge and decreases P. acnes-induced elevation of cytokine production. This review highlights the potential functions of killed P. acnes- and sialidase-based vaccines as novel treatments for P. acnes-associated diseases.