Adjuvant therapy for severe sepsis and shock can be divided into 4 groups. The first group comprises those compounds with proven efficacy in human studies (activated protein C and recombinant bacterial permeability-increasing protein). The second group includes compounds with potential efficacy (heparin), while the third group represents those with no demonstrated efficacy in randomised clinical trials (tumour necrosis factor and interleukin-1 antibodies and receptor antagonists). The fourth group includes those drugs which have been found to be potentially effective in animal studies, but which have not yet been evaluated in humans (i.e., tyrosine kinase inhibitors, selective inducible nitric oxide synthase inhibitors, polyadenosine-diphosphate-ribose-polymerase and caspase III (apoptosis) inhibitors). Formal clinical comparisons between the various treatment options are necessary to assist the clinician in selecting the appropriate form of therapy.