<b><i>Background:</i></b> The incidence of anal cancer has increased over at least the past decade, with estimates of a continued increase in the coming years. Women are more commonly affected than men in the general population; separate high-risk populations have also been identified. While the pathophysiology of anal cancer is thought to be similar to its cervical counterpart, well-defined and standardized screening guidelines have not been established as is seen in cervical cancer prevention. Nonetheless, multiple screening modalities have been examined and are components of proposed institutional and societal screening programs. <b><i>Summary:</i></b> Anal cytology is one modality that is a mainstay of many suggested screening guidelines. Interpretation and reporting follow current criteria for cervical/vaginal cytology per the Bethesda System, with site-specific alterations and changes in adequacy criteria to better accommodate some of the confounding factors encountered in anal cytology. While there are some limitations, such as a tendency to underestimate the degree of dysplasia and variable interobserver concordance rates, anal cytology, especially liquid-based preparations, overall performs well in detecting anal abnormalities and acts as an adequate screening tool. Importantly, most anal squamous dysplasias and cancers are also associated with human papillomavirus (HPV) infection, raising the possibility of HPV testing or genotyping as a component of screening and/or follow-up. Studies have also shown the efficacy of HPV vaccination in preventing anal lesions. Digital anorectal exam as well as anoscopy, particularly high-resolution anoscopy, are also often components of screening and follow-up. Management guidelines such as those put forth by the American Society for Colposcopy and Cervical Pathology (ASCCP) for cervical cancer are also not established for anal cancer. However, studies such as the Anal Cancer HSIL Outcomes Research (ANCHOR) trial have made significant strides in demonstrating successes in follow-up and treatment of anal lesions, findings that are crucial for establishing prevention and management guidelines going forward.