Human papillomavirus (HPV) is a well-studied etiologic agent for cervical cancer dysplasia and neoplasia. HPV E6 and E7 viral proteins drive oncogenesis by blocking the activity of pRB and p53, respectively. Consensus screening guidelines focus on appropriate use of both cervical cytology and HPV testing to reduce the morbidity and mortality associated with cervical cancer. HPV testing is indicated for women aged 21 to 64 years with atypical squamous cells of undetermined significance (ASC-US) on cytology. In women aged 30 to 64, testing is also indicated for routine screening in conjunction with cervical cytology. Various methods are available for HPV detection and several Food and Drug Administration-approved assays are on the market using either signal or target amplification methodologies. Most of the approved tests target DNA, but tests for mRNA detection are also available. Recently, assays for type specific detection of HPV types 16 and 18 have been Food and Drug Administration approved, and the use of genotyping has been incorporated into management algorithms. HPV testing can be performed on liquid-based cytology samples and options for automation are available making the introduction of HPV testing into many pathology laboratories possible.