Human papillomavirus (HPV) infection can affect the urethra of male and female individuals causing symptoms and concern. Urethral lesions (warts) may occasionally develop and the urethra can also be a source of HPV infection, contributing to the spread of infection between partners. This chapter reviews updated concepts concerning urethral HPV, including new detection methods, treatment options, and prevention. In addition, the role of HPV in the development of urethral, bladder, prostate, and kidney cancer is also discussed. The prevalence of urethral involvement among genital HPV-associated lesions is 4–25% (von Krogh, 2001) and the prevalence of HPV detection in the urethra, in the absence of clinical lesions, ranges from 3 to 50% (Rosemberg et al., 1988; Katelaris et al., 1988; Cecchini et al., 1988; Aynaud et al., 2003). Chuang et al. (1984) reported that the male ­urethra is affected more often than the female urethra, and recent analysis by von Krogh (2001) reported HPV-related meatal lesions in 20–25% of male and 4–8% of female individuals. Meatal warts have also been observed in children, and Takatsuki et al. (1993) described a relapsing meatal condyloma in a 4-year-old boy.