Trypanosomatids parasites are causative agents of important neglected tropical diseases, such as leishmaniasis and Chagas disease. In the absence of an effective and safe vaccine, the main strategies currently available for the control of these diseases are chemotherapy whit drugs limited by their cost, toxicity, long time of treatment, and by emergence of resistant parasites. Therefore, in silico methods have arisen in the last years as powerful tools to optimize the search for new drugs and targets and for potential antigens for vaccines. In this context, the aim of this chapter is to provide the reader with important tools in use for drug design, particularly for molecular docking and epitope prediction for vaccines, in order to make useful to put this concepts and approaches in practice. All these tools should be applied in the fight against trypanosomatids.