Transmission of disease agents by arthropods is a complex phenomenon, including relationships among the various arthropod vectors, their pathogens, and their animal hosts. Myriad factors affect the ability of arthropods to acquire, maintain, and ultimately transmit pathogens. This chapter presents an in-depth discussion of the concept of vector competence and the various ways arthropods acquire and transmit disease agents. Mechanical transmission of disease agents occurs when arthropods merely physically transport pathogens from one place or host to another one, while biological transmission is much more complex, occurring when the disease agent undergoes changes in form or multiplies within its arthropod vector.