Propionibacterium acnes is a Gram-positive bacterium that is intimately associated with humans. The nature and consequences of this symbiosis are poorly understood; it might comprise both mutualistic and parasitic properties. Recent advances in distinguishing phylotypes of P. acnes have revealed that certain type I lineages are predominantly associated with acne vulgaris. Genome analyses revealed a highly conserved core genome and the existence of island-like genomic regions and possible mobile genetic elements as part of the flexible gene pool. The analysis of clustered regularly interspaced short palindromic repeats (CRISPR), found exclusively in type II P. acnes, recently revealed the presence of CRISPR spacers that derived from mobile genetic elements. These elements are present in a subset of P. acnes type I lineages. Their significance for type-specific host-interacting properties and their contribution to pathogenicity is currently under investigation.