Published literature describing the use of oral ivermectin for the treatment of head lice infestation is reviewed.In the United States and globally, head lice infestation, or pediculosis capitis, remains a public health issue with both social and medical implications. Treatment with oral or topical medications is typically required for head lice eradication. Resistance to traditional topical therapies for head lice infestation is increasing, creating a need for consideration of additional treatment options. A growing body of data describing the potential role of oral ivermectin for the treatment or prevention of head lice infestation is available. A literature search identified 5 clinical trials that evaluated safety and/or effectiveness outcomes of oral ivermectin use as an alternative to malathion, other topical prescription medications, and traditional, nonprescription remedies; those studies were conducted in various parts of the world (e.g., Australia, Brazil, Mexico, Egypt) and likely involved varying types and degrees of lice resistance. Clinical research findings to date, while not consistently robust, suggest that oral ivermectin is comparable or superior in effectiveness to other topical treatment options for head lice infestation while being well tolerated and favorably perceived by patients and caretakers.Oral ivermectin is an option for the treatment of head lice infestation, especially in individuals who have experienced a treatment failure. Published evidence from clinical trials indicates that oral ivermectin is as effective as currently available topical treatments.