Schistosomiasis is one of the most serious parasitic diseases. More than 250 million people are infected with schistosomes in the tropics or subtropics. The parasitic flukes have some unique biological features: dioecism, complex life cycles, mechanisms to avoid host immune responses, and an apparent reliance on host endocrine and immune signals to complete their development, maturation and egg production. Recently, a large dataset of expressed sequence tags (ESTs) were generated from Schistosoma japonicum and Schistosoma mansoni, from which numerous novel genes were identified. The transcriptome analyses provide the basis for a comprehensive understanding of the molecular mechanisms involved in schistosome nutrition and metabolism, host-dependent development and maturation, immune evasion and invertebrate evolution. In addition, new potential vaccine candidates and drug targets have been predicted.