One of the long-lasting open questions in understanding acne is the role of the skin bacterium Propionibacterium acnes. Opinions within the scientific community diverge regarding the importance of this Gram-positive bacterium not only in acne but also in other P. acnes-associated diseases. The recently decoded genome gives us some clues with respect to its pathogenic potential and its strategies to survive in the harsh environment of human skin. This review focuses on the major findings of the genome sequence. Special attention has been drawn to the cell surface composition of P. acnes, its antigenic potential, and to enzymes that are potentially involved in degrading skin-derived substances.