Septic syndromes are the main cause of death in the intensive care units and although the mortality rates is slowly decreasing, the occurrence of the disease has been increasing. The pathogenesis of sepsis includes countless disturbances of the host immune system starting with a harmful, infection-triggered exaggerated inflammatory cascade, followed by the development of an immunoparalysis state. The latter contributes to the failure in pathogen eradication and leads to secondary infections, which are often the cause of fatal complications. In this review, we consider different novel therapeutic strategies for restoration of immune function. The use of glucocorticoids, intravenous immunoglobulins, heparin, recombinant human activated protein C, granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor, interferon-γ, statins, macrolides and high-volume hemofiltration are discussed. Even though some clinical trials of these regimens are promising, the key to their successful application seems to be the precise monitoring of the status of immune system followed by implementation of the adequate therapy. Thus, in this paper we present disturbances in the immune system in the course of human sepsis, with special attention to the parameters that could be monitored and serve as markers for immunomodulatory therapies. We conclude by briefly presenting the current sepsis treatment strategy.