Background: Rickettsiosis is a potential life threatening infectious disease in travelers. Clinical recognition is not always straightforward, as typical manifestations such as rash and/or eschar may be absent. Definite diagnosis is based on seroconversion and therefore often delayed until the convalescent phase of disease. Case presentation: In this case report, we describe four patients with severe travel-related rickettsiosis (two patients with murine-and two patients with scrub typhus), in whom acute-phase diagnosis was possible by real-time polymerase chain reaction on serum or blood. Conclusions: Despite its limitations, we think that polymerase chain reaction can contribute significantly to the early diagnosis and treatment of rickettsial disease in travelers.