Sand flies are delicate, gnat-like flies in the family Psychodidae which feed on a variety of mammals and sometimes other vertebrates such as reptiles and amphibians. Many species are significant public health nuisance pests and vectors of disease. This chapter explores the ecology and disease potential of sand flies, including discussion of the major sand fly species worldwide. Finally, the diseases leishmaniasis, bartonellosis, and sandfly fever are presented and discussed, including their geographic distributions, sand fly vectors, and comments about their treatment, prevention, and control.