The use of minimally invasive procedures for diagnosis and treatment decisions means that very often cytological samples are the only material available for testing. Cytology has evolved from a strictly morphological approach to the routine use of immunohistochemistry. The advent of personalized medicine has increased the demand for molecular testing, making rapid on-site evaluation even more relevant. This article presents current rapid on-site evaluation practice patterns in different settings, with a special focus on the variety of professionals involved. Technological advances such as telepathology can help to alleviate distance constraints. This article also provides an overview of telecytopathology, describing challenges to its implementation and how to address them. Issues such as hardware, personnel training, communication, guidelines, validation, use, and future directions are highlighted. Cancer Cytopathol 2017;125(6 suppl):449-54.