Staphylococcus haemolyticus is one of the most frequent aetiological factors of staphylococcal infections. This species seems to lack the important virulence attributes described in other staphylococci. However, studies have shown that the presence of various enzymes, cytolysins and surface substances affects the virulence of S. haemolyticus. Nevertheless, none of them has been identified as crucial and determinative. Despite this, S. haemolyticus is, after Staphylococcus epidermidis, the second most frequently isolated coagulase-negative staphylococcus from clinical cases, notably from blood infections, including sepsis. This raises the question of what is the reason for the increasing clinical significance of S. haemolyticus? The most important factor might be the ability to acquire multiresistance against available antimicrobial agents, even glycopeptides. The unusual genome plasticity of S. haemolyticus strains manifested by a large number of insertion sequences and identified SNPs might contribute to its acquisition of antibiotic resistance. Interspecies transfer of SCCmec cassettes suggests that S. haemolyticus might also be the reservoir of resistance genes for other staphylococci, including Staphylococcus aureus. Taking into consideration the great adaptability and the ability to survive in the hospital environment, especially on medical devices, S. haemolyticus becomes a crucial factor in nosocomial infections caused by multiresistant staphylococci.