Staphylococcal infections cause a number of serious diseases, ranging from acute septicaemia to chronic problems such as osteomyelitis and septic arthritis. Resistance to antibiotics is a growing problem and has re-ignited interest in vaccines and in passive immunization with antibodies. Natural infections and vaccines based on whole bacteria lead to poor antibody responses, but recent research using animal models of several staphylococcal diseases reveals that vaccines based on recombinant staphylococcal extracellular-matrix-binding proteins are much more protective. Passive immunization with antibodies against one of these proteins (collagen-binding protein) also shows promise in a mouse model of sepsis.