Strongyloides stercoralis hyperinfection syndrome (SHS) is a life-threatening condition that warrants early detection and management. We describe the pathogenesis, organ-specific clinical manifestations, and risk factors associated to this condition. A comprehensive review of the literature was conducted in PubMed, LILACS, EBSCO and SciELO by using the keywords: “hyperinfection syndrome”; “Strongyloides stercoralis”; “disseminated strongyloidiasis”; “systemic strongyloidiasis”, “pathogenesis” and “pathophysiology”. Relevant articles on this topic were evaluated and included by consensus. Also, a secondary search of the literature was performed. Articles in English and Spanish language were included. SHS has been described in tropical and sub-tropical regions. However, there is growing evidence of cases detected in developed countries favored by increasing migration and the advance in immunosuppressive therapies for oncologic and inflammatory diseases. SHS is characterized by massive multiplication of larvae, typically in immunocompromised hosts. Clinical manifestations vary according to the organ involved and include diarrhea, intestinal bleeding, alveolar hemorrhages, heart failure, jaundice, bacteremia among others. Despite advances in the understanding of this condition, fatality rates are near 90%. Clinicians should consider SHS in the differential diagnosis of acutely ill patients with multiple organ damage and epidemiological risk factors. Adverse outcomes are common, especially with delayed anti-parasitic treatment.