The incorporation of digital pathology into routine pathology practice is becoming more widespread. Definite advantages exist with respect to the implementation of artificial intelligence (AI) and deep learning in pathology, including cytopathology. However, there are also unique challenges in this regard. This review discusses cytology-specific challenges, including the need to implement digital cytology prior to AI; the large file sizes and increased acquisition times for whole slide images in cytology; the routine use of multiple stains, such as Papanicolaou and Romanowsky stains; the lack of high-quality annotated datasets on which to train algorithms; and the considerable computer resources required, in terms of both computer infrastructure and skilled personnel, for computing and storage of data. Global concerns regarding AI that are certainly applicable to cytology include the need for model validation and continued quality assurance, ethical issues such as the use of patient data in developing algorithms, the need to develop regulatory frameworks regarding what type of data can be utilized and ensuring cybersecurity during data collection and storage, and algorithm development. Key Messages: While AI will likely play a role in cytology practice in the future, applying this technology to cytology poses a unique set of challenges. A broad understanding of digital pathology and algorithm development is desirable to guide the development of algorithms, as well as the need to be cognizant of potential pitfalls to avoid when incorporating the technology in practice. © 2020 S. Karger AG, Basel.