The outer membrane is the first line of contact between Gram-negative bacteria and their external environment. Embedded in the outer membrane are integral outer membrane proteins (OMPs) that perform a diverse range of tasks. OMPs are synthesized in the cytoplasm and are translocated across the inner membrane and probably diffuse through the periplasm before they are inserted into the outer membrane in a folded and biologically active form. Passage through the periplasm presents a number of challenges, due to the hydrophobic nature of the OMPs and the choice of membranes into which they can insert. Recently, a number of periplasmic proteins and one OMP have been shown to play a role in OMP biogenesis. In this review, we describe what is known about these folding factors and how they function in a biological context. In particular, we focus on how they interact with the OMPs at the molecular level and present a comprehensive overview of data relating to a possible effect on OMP folding yield and kinetics. Furthermore, we discuss the role of lipo-chaperones, i.e. lipopolysaccharide and phospholipids, in OMP folding. Important advances have clearly been made in the field, but much work remains to be done, particularly in terms of describing the biophysical basis for the chaperone–OMP interactions which so intricately regulate OMP biogenesis.