Neglected tropical diseases caused by trypanosomatid parasites are a continuing and escalating problem, which devastate the less economically developed cultures in countries in which they are endemic by impairing both human and animal health. Current drugs for these diseases are regarded as out-of-date and expensive, with unacceptable side-effects and mounting parasite resistance, meaning there is an urgent need for new therapeutics. Natural products have long been a source of potent, structurally diverse bioactive molecules. Herein are reviewed natural products with reported trypanocidal activity, which have been clustered based on core structural similarities, to aid the future discovery of new trypanocidal core motifs with potential routes to synthetically accessible natural product cores suggested.