Contrary to the widespread belief that severe malaria is mainly caused by Plasmodium falciparum, malaria caused by Plasmodium vivax infection may also lead to severe clinical manifestations including a plethora of renal, pulmonary, hematologic, neurologic, and multiorgan dysfunction. Anemia and thrombocytopenia are considered as two major important markers of severity during the clinical course of severe P. vivax malaria. In highly endemic areas of P. vivax transmission, early diagnosis is crucial in preventing uncomplicated episodes progressing into severe and complicated clinical forms. In fact, given the wide geographic distribution of P. vivax, there is a large burden of disease, often not adequately acknowledged, and resulting from the combined effect of the large numbers of uncomplicated clinical episodes and the increasingly recognized severe and complicated clinical presentations.