Selecting the appropriate antimicrobial agent for reptiles is based on similar principles and considerations common to antimicrobial selection in domestic species. This chapter focuses on the process of antimicrobial selection in reptiles while highlighting the unique differences and challenges associated with selecting antimicrobial agents for these species. Due to the lack of pharmacokinetic studies, the chapter also focuses on bacterial and mycotic pathogens. The size and temperament of a reptile can influence antimicrobial drug selection and the route of administration. The chapter provides initial suggestions for differential diagnosis that should always be followed with attempts to obtain a definitive diagnosis. Finally, the clinician needs to review the available pharmacokinetic studies in reptiles and carefully consider the most appropriate antimicrobial drug selection given the available evidence.