Changes of the immune system can be a consequence of an underlying malignancy or induced by antineoplastic treatment. Both influence the risk for infectious complications and relapse. Over the past decade, there have been a series of major developments in the laboratory assessment of immune dysfunction, particularly as it relates to the complex interactions of the distinct components of the immune system. In addition, several new therapeutic strategies that modulate the immune system have been introduced. We review new findings that can affect clinical decision making. Better insights into the impairment of host response could provide the rationale for the development of new therapeutic strategies, for both supportive care and anticancer treatment.