The skin commensal Propionibacterium acnes, recently renamed Cutibacterium acnes, along with the other major pathophysiological factors of increased seborrhea, hyperkeratinization of the pilosebaceous unit, and inflammation, has long been implicated in the pathogenesis of acne. Recent advances have contributed to our understanding of the role of P. acnes in acne. Although there are no quantitative differences in P. acnes of the skin of patients with acne compared with controls, the P. acnes phylogenic groups display distinct genetic and phenotypic characteristics, P. acnes biofilms are more frequent in acne, and different phylotypes may induce distinct immune responses in acne. P. acnes plays a further important role in the homeostasis of the skin’s microbiome, interacting with other cutaneous commensal or pathogenic microorganisms such as Staphylococcus epidermidis, Streptococcus pyogenes, and Pseudomonas species. In the era of increasing antimicrobial resistance, the selection of acne treatment targeting P. acnes and the prevention of antibiotic resistance play a key role in improving outcomes in acne patients and public health.