Schistosomiasis is a neglected tropical disease that affects more than 240 million individuals throughout the world. Praziquantel and oxamniquine are the only drugs available for the control of schistosomiasis. Our dependence on just two drugs and concerns about tolerance and/or resistant schistosome strains emphasize the need for developing new schistosomicidal drugs. This chapter summarizes recent reports about schistosomicidal activity of natural products against Schistosoma species. The in vitro and in vivo effects of a number of crude plant extracts, essential oils, and several secondary metabolites (including alkaloids, flavonoids, and lignans) on schistosoma are summarized and discussed. Particular emphasis is placed on in vivo studies and on works describing the direct in vitro effects of natural products on the parasite (schistosomula and adult stages). Some interesting results with promising samples have already been obtained, but more research is required to discover an ideal natural schistosomicidal lead candidate.