Tropical infections form 20–30% of ICU admissions in tropical countries. Diarrheal diseases, malaria, dengue, typhoid, rickettsial diseases and leptospirosis are common causes of critical illness. Overlapping clinical features makes initial diagnosis challenging. A systematic approach involving (1) history of specific continent or country of travel, (2) exposure to specific environments (forests or farms, water sports, consumption of exotic foods), (3) incubation period, and (4) pattern of organ involvement and subtle differences in manifestations help in differential diagnosis and choice of initial empiric therapy. Fever, rash, hypotension, thrombocytopenia and mild derangement of liver function tests is seen in a majority of patients. Organ failure may lead to shock, respiratory distress, renal failure, hepatitis, coma, seizures, cardiac arrhythmias or hemorrhage. Diagnosis in some conditions is made by peripheral blood smear examination, antigen detection or detection of microbial nucleic acid by PCR. Tests that detect specific IgM antibody become positive only in the second week of illness. Initial therapy is often empiric; a combination of intravenous artesunate, ceftriaxone and either doxycycline or azithromycin would cover a majority of the treatable syndromes. Additional antiviral or antiprotozoal medications are required for some specific syndromes. Involving a physician specializing in tropical or travel medicine is helpful.