Splendore-Hoeppli phenomenon (asteroid bodies) is the in vivo formation of intensely eosinophilic material (radiate, star-like, asteroid or club-shaped configurations) around microorganisms (fungi, bacteria and parasites) or biologically inert substances. This study presents a literature review concerning Splendore-Hoeppli reaction in the mucocutaneous diseases. It examines the histopathological features, nature and differential diagnosis of this reaction. It also discusses the mucocutaneous infections and the non-infective diseases associated with it. Available studies indicate that several mucocutaneous infections can generate Splendore-Hoeppli reaction. The fungal infections include sporotrichosis, pityrosporum folliculitis, zygomycosis, candidiasis, aspergillosis and blastomycosis. The bacterial infections include botryomycosis, nocardiosis and actinomycosis. The parasitic conditions include orbital pythiosis, strongyloidiasis, schistosomiasis and cutaneous larva migrans. In addition, Splendore-Hoeppli reaction may be seen with non-infective pathology such as hypereosinophilic syndrome and allergic conjunctival granulomas. The Splendore-Hoeppli reaction material comprises antigen-antibody complex, tissue debris and fibrin. Although the exact nature of this reaction is unknown, it is thought to be a localized immunological response to an antigen-antibody precipitate related to fungi, parasites, bacteria or inert materials. The characteristic formation of the peribacterial or perifungal Splendore-Hoeppli reaction probably prevents phagocytosis and intracellular killing of the insulting agent leading to chronicity of infection. To conclude, Splendore-Hoeppli reaction is a tell tale of a spectrum of infections and reactive conditions. The molecular pathways involved in the development of this reaction are open for future investigations.