Although infections caused by the straminipilan pathogen Pythium insidiosum were described in 19th century, it has been only recently that its epidemiology, immunology, treatment and other important traits were extensively studied. These studies were of paramount importance to theorize about the ecological niche for this pathogen, its host-parasite relationships, the antigens used for diagnosis, and the management of the infection using immunotherapy. P. insidiosum triggers in the infected host a T helper 2 [Th2] subset with an inflammatory reaction composed mainly of eosinophils and mast cells. These cells degranulate around the hyphal elements of P. insidiosum where a Splendore-Hoeppli-like reaction develops. In horses this reaction is so intensive that firm concretions called 'kunkers' develop. These data indicated that this pathogen might have developed an evolutionary strategy to conceal important antigens from the host immune system. Immunotherapy, a treatment approach that relies on the injection of antigens of P. insidiosum from in vitro cultures, has been successfully used in humans and horses to manage this disease. A switch from a Th2 to Th1 response is postulated as the most likely explanation of the curative properties of this approach. This review provides details on the serological, immunological, and immunotherapeutic methodologies used to diagnose and treat the infections caused by this pathogen.