The classical model of the biofilm cycle: the four-step process of biofilm formation in S. aureus. Planktonic cells adhere to the biomaterial surface through AtlA adhesin. Then, MSCRAMMs and SERAMs bacterial adhesins interact with the extracellular matrix (ECM) proteins coating the implant. Bacteria proliferate and produce an extracellular polymeric substance consisting of proteins (among which is the biofilm-associated protein Bap), the intercellular polysaccharide adhesin (PIA), and a series of other polymeric extracellular substances, among which is extracellular DNA (eDNA). Once a mature biofilm has formed, under the control of the quorum sensing system, the enzymes β-phenol-soluble modulins, proteases, and murein hydrolases dissolve biofilm and release planktonic bacteria to initiate a new biofilm cycle. The more recently emerged role of the microenvironment and host molecules in biofilm formation is also recalled. Abbreviations: AtlA, the major autolysin of S. aureus; EPS, extracellular polymeric substance; MSCRAMMs, Microbial Surface Components Recognizing Adhesive Matrix Molecules; SERAMs, Secretable Expanded Repertoire Adhesive Molecules.