Spores and fungal fragments found in indoor and outdoor environments originate from opportunistic fungi and they can contribute to inflammatory responses, causing a broad range of symptoms. Papers were selected and reviewed with an emphasis on the molecular mechanisms involved in the effect of fungi on immune cells, especially mast cells (MCs). Fungi can bind to antibodies and complement them, allowing them to be recognized by cells of the innate immune system, including macrophages, dendritic cells, and MCs, which are then stimulated via Toll-like receptor signaling. Fungi can cause diseases mediated by MCs and aggravate allergic inflammation. Immunosuppressed subjects can be particularly susceptible to developing diseases caused by opportunistic fungi. Mold also liberates mycotoxins that could be on volatile spores and stimulate MCs to secrete pro-inflammatory cytokines/chemokines, but this mechanism is not known. Fungi can activate the immune system directly or through mycotoxins, leading to stimulation of immune cells and chronic neuroinflammatory symptoms. Some of these processes may be inhibited by the new anti-inflammatory cytokine interleukin 37.