This chapter provides an overview of the different in vitro and in vivo strategies to progress a new compound for visceral leishmaniasis from early screening, through in vivo testing and potential translation, to clinical development, including the value of novel pharmacokinetic–pharmacodynamic modelling and simulation tools to support this transition. The case of miltefosine, the only oral drug currently available for leishmaniasis, is presented to demonstrate how pharmacokinetic–pharmacodynamic modelling and simulation can provide new insights into how to optimize currently available drugs, such as the use of allometric dosing of miltefosine to overcome the lower drug exposure in children and the practical example of the clinically recommended minimal duration of contraception for female patients of child-bearing age.