Swainsonine, an indolizidine alkaloid with significant physiological activity, is an α-mannosidase and mannosidase II inhibitor that alters glycoprotein processing and causes lysosomal storage disease. Swainsonine is present in a number of plant species worldwide and causes severe toxicosis in livestock grazing these plants. Consumption of these plants by grazing animals leads to a chronic wasting disease characterized by weight loss, depression, altered behavior, decreased libido, infertility, and death. This review focuses on the three plant families and the associated taxa that contain swainsonine; the fungi that produce swainsonine, specifically the fungal endophytes associated with swainsonine-containing taxa; studies investigating the plant, endophyte, and swainsonine relationship; the influence of environmental factors on swainsonine concentrations in planta; and areas of future research.