The ongoing 2022 monkeypox virus outbreak has disproportionately impacted men who have sex with men and is associated with an increased frequency of atypical symptoms. The impetus for this outbreak is currently unknown. Experts suggest it may be related to the cessation of routine smallpox vaccination globally and biological changes in the monkeypox virus itself. Human monkeypox infection is classically associated with a fever prodrome followed by the eruption of small macules at the site of inoculation and when disseminating. The lesions then develop into a papule within 1-2 days and turn it a vesicle that pustulate with central umbilication within 5-7 days. They may ulcerate as they heal but will eventually begin to scab and new skin will form which often leaves a hyperpigmented or pitting scar. The overall process can take 2-3 weeks to heal entirely depending on the immune status of the host and other factors, such as antiviral treatment and previous vaccination. Primary inoculation of the monkeypox virus in the perianal region can lead to the development of single or multiple vesiculopustular lesions. They can appear similar to other sexually transmitted infections which could lead to a misdiagnosis. We present two separate cases of human monkeypox infection in men who have sex with men and concomitant human immunodeficiency virus (HIV) disease who both presented for anogenital lesions and proctitis who were successfully treated with tecovirimat. Treatment with tecovirimat has been shown to reduce symptoms and duration of illness. However, the unique features of the 2022 monkeypox virus outbreak necessitate further research to better understand the efficacy of this antiviral in the current monkeypox outbreak.